Determinants of the incidence and severity of ventricular arrhythmias in aortic valve disease

The incidence of ventricular arrhythmias in patients with aortic valve disease was investigated. Twenty-four-hour ambulatory electrocardiographic recordings were obtained in 93 patients without coronary artery disease (aortic stenosis [AS], n = 38; combined AS and aortic regurgitation [AR], n = 27; and AR only, n = 28). The arrhythmias were compared with the hemodynamic findings of cardiac catheterization. Ventricular premature beats (VPB) were noted in 78 patients (84%). They were rare (< 100 VPB/22 hours) in 40 patients (43%), moderately frequent (101 to 1,000 VPB/22 hours) in 23 patients (25%), and frequent (> 1,000 VPB/22 hours) in 15 patients (16%). Multiformity was found in 47 (51%), paired VPB in 32 (34%), and ventricular tachycardia in 17 (18%) of the 93 patients studied. The occurrence of ventricular arrhythmia was not related to the type of valve lesion, to the transvalvular gradient in patients with AS, or to the degree of regurgitation in patients with AR. In contrast, the grade of arrhythmia showed a negative correlation with left ventricular ejection fraction (AS, r_s = ?0.58; AS and AR, r_s = ?0.67; AR, r_s = ?0.78; all p < 0.001) and a positive correlation with peak systolic left ventricular wall stress (AS, r_s = 0.56; AS and AR, r_s = 0.56; AR, r_s = 0.57; all p < 0.001). The frequency of VPB also showed a negative correlation with left ventricular ejection fraction (AS, r_s = ?0.63; AS and AR, r_s = ?0.65; AR, r_s = ?0.71; all p < 0.001).This study indicates that ventricular arrhythmias are present in a large number of patients with aortic valve disease. The severity of arrhythmias is strongly influenced by myocardial performance. Thus, severe arrhythmias are frequently a sign of impaired left ventricular function.     

Coronary dilatory capacity in idiopathic dilated cardiomyopathy: Analysis of 16 patients

Hemodynamic function and overall coronary blood flow (argon technique) were measured in 16 patients with idiopathic dilated cardiomyopathy (IDC) and in 12 patients without detectable heart disease (control subjects) referred for precordial pain. In patients with IDC, coronary blood flow was normal at rest (78 ± 17 ml/100 g·min versus 78 ± 9 in control subjects). During maximal inducible coronary vasodilation (dipyridamole, 0.5 mg/kg), coronary blood flow was significantly reduced (142 ± 38 ml/100 g · min versus 301 ± 64 in control subjects; p < 0.001). Consequently, obtainable minimal coronary resistance was increased in IDC (0.54 ± 0.20 mm Hg/ml/100 g · min versus 0.23 ± 0.04 in control subjects; p < 0.001). In patients with IDC, left ventricular (LV) end-diastolic pressure was significantly increased (19 ± 11 mm Hg versus 6 ± 3 in control subjects; p < 0.005), and the LV ejection fraction was diminished (36 ± 11% versus 72 ± 3% in control subjects; p < 0.001). In patients with IDC, LV end-diastolic pressure correlated significantly with the obtained minimal coronary resistance after application of dipyridamole (r = 0.85; p < 0.001). LV catheter biopsy specimens revealed no alterations in myocardial microvasculature. Thus, coronary dilatory capacity is impaired in patients with IDC, due partially to an increase in extravascular component of coronary resistance.     

Effect of prolonged exercise on serum lipids and lipoproteins

It has been shown that physical exercise lowers serum triglyceride levels and may increase high density lipoprotein-cholesterol levels. Understanding of the mechanisms responsible for these beneficial adaptations is still incomplete. Twenty-six men, who played soccer continuously for 64 hours to establish a world's record, were monitored for acute changes in lipid metabolism. Food intake was determined before and during the exercise period. Blood specimens were taken before and repeatedly during the match for the measurement of triglycerides (TG), total cholesterol (CH), glycerol, apolipoprotein A-I (apoA-I), and cholesterol in various lipoprotein fractions (quantitative lipoprotein electrophoresis). During exercise TG levels decreased from 116 +/- 26 to 66 +/- 13 mg/dL and CH from 180 +/- 22 to 135 +/- 25 mg/dL. Both TG and glycerol showed an initial increase followed by a continuous decrease. Alpha-CH increased by 19% whereas beta-CH and pre-beta-CH decreased markedly (39% and 78%, respectively). In contrast to alpha-CH, apo A-1 fell only slightly by 10%. These results indicate that the effect of chronic exercise on lipids and lipoproteins can be mimicked by acute prolonged exercise. Similar mechanisms may be involved in these adaptations. Moreover, the extreme length of physical exertion substantially lowered CH.     

Intracoronary thrombolysis in acute myocardial infarction: Duration of ischemia as a major determinant of late results after recanalization

To define the effect of duration of myocardial ischemia on the late results after successful thrombolysis in patients with acute transmural myocardial infarction, data on 39 patients treated with intracoronary infusion of streptokinase were analyzed. Patients with successful recanalization of infarct vessel and a time lag between onset of symptoms and reperfusion less than 4 hours were assembled in group A1 (n = 15) and patients with successful recanalization but a time lag of more than 4 hours (n = 17) in group A2. Group B consisted of 7 patients with unsuccessful thrombolysis. Coronary anatomy, left ventricular volume, ejection fraction and regional ejection fraction of infarct area were determined before and 4 weeks after thrombolysis with cineangiography. Serum creatine kinase activity was serially measured.Before intervention, the groups were comparable with regard to age, Killip class, localization of infarction, incidence of previous infarction, Gensini score of coronary anatomy, left ventricular volume, ejection fraction, regional ejection fraction of infarct area and serum creatine kinase activity. Four weeks after the intervention, patients in group A1 had a higher ejection fraction (59 %) and regional ejection fraction of infarct area (39%) than patients in group A2 (ejection fraction: 49%, p < 0.05; regional ejection fraction: 26%, p < 0.05) and group B (ejection fraction: 44%, p < 0.05; regional ejection fraction: 25%, p = 0.05). Peak serum creatine kinase activity measured during the acute illness was lower in group A1 (764 U/liter) than in group A2 (1,580 U/liter, p < 0.05) and group B (2,106 U/liter, p < 0.05).Thus, contraction of infarct area was improved and enzymatic estimate of infarct size was reduced after early as compared with late reperfusion in patients with acute myocardial infarction.     

Effect of successful thrombolytic therapy on right ventricular function in acute inferior wall myocardial infarction

In 19 patients undergoing intracoronary fibrinolytic therapy for acute myocardial infarction, the site of coronary obstruction was in the proximal right coronary artery. Time between onset of symptoms and hospitalization was less than 4 hours. These patients were studied prospectively by radionuclide techniques immediately after admission, 48 hours and 4 weeks after AMI. Right and left ventricular (RV and LV) ejection fractions (EF) were calculated from gated blood pool scintigrams and the size of the LV perfusion defect was assessed by thallium-201 scintigraphy. Before the intervention, RV performance was significantly lower (RVEF 29 +/- 8%) than normal (53 +/- 7%). The size of the LV perfusion defect was relatively small (less than 25% of LV circumference), and as a consequence, LV pump function was only marginally impaired (LVEF 54 +/- 11%). Recanalization of the infarct artery was achieved in 12 patients (group A); in 7 patients the infarct artery remained occluded (group B). Early after the intervention (48 hours), RV performance in group A recovered significantly (RVEF: 30 +/- 9% vs 39 +/- 7%, p less than 0.01), and further improvement was noted at 4 weeks (RVEF 43 +/- 5%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

High serum chromium levels after cardiac valve replacement: Clinical significance and metabolic effects

Serum and red blood cell concentrations of the trace elements chromium and manganese were determined in 66 patients who underwent cardiac valve replacement and in 40 control subjects. Patients with a Starr-Edwards metallic ball prosthesis had serum chromium levels of 2.54 ± 0.20 ng/ml (mean ± standard error of the mean), exceeding widely the Normal limits (0.43 ± 0.03 ng/ml, p < 0.001). The red cell chromium content in these patients (9.9 ± 0.4 ng/ml) was only 15 percent higher than control values (p < 0.05). Patients without evidence of prosthetic valve incompetence had a significant decrease in serum chromium toward normal levels during the postoperative period (p < 0.001). This decrease appeared to be delayed and reduced in patients with a perlprosthetic leak. Chromium levels in patients with a Starr-Edwards plastic ball or Björk-Shiley prosthesis did not differ significantly from control values. There was no significant difference in manganese levels between the groups.To study metabolic effects of changes in serum chromium, fasting cholesterol, triglyceride and glucose plasma concentrations were determined in 27 patients with a Starr-Edwards metallic ball prosthesis and in 29 patients with a Starr-Edwards plastic ball or Björk-Shiley prosthesis before and after valve replacement. In both groups, an increase In both cholesterol and triglyceride concentrations was observed regardless of the presence or absence of elevated serum chromium levels. Glucose concentrations remained unchanged after surgery. It is concluded that (1) elevation of serum chromium levels does not appear to cause a decrease of fasting lipid and glucose concentrations; and (2) there is no evidence that in the sample of patients studied a chromium deficiency may play an important role in the development of elevated lipid and glucose levels.     

Intracoronary thrombolysis in acute myocardial infarction: An attempt to quantitate its effect by comparison of enzymatic estimate of myocardial necrosis with left ventricular ejection fraction

The quantity of myocardium was estimated that can be salvaged by reperfusion of acute transmural myocardial infarction (MI). Serial analysis of serum creatine kinase (CK) activity was carried out in 41 consecutive patients with acute MI who underwent intracoronary thrombolysis. Enzymatic estimate of MI size was calculated using an average (method A) and an individually determined elimination constant (method B). Left ventricular ejection fraction 4 weeks after successful thrombolysis (cineangiogram) correlated inversely with MI size (method A: r = −0.85, method B: r = -0.76; both p < 0.001). Patients with recanalization within 4 hours after the onset of symptoms were assembled in group A₁ (n = 13, early reperfusion), and patients with successful recanalization after 4 hours in group A₂ (n = 16, late reperfusion). Group B consisted of 12 patients without reperfusion. MI size in group A₁ was 21 CK-g-Eq (method A) and 23 CK-g-Eq (method B), in group A₂ 50 CK-g-Eq (method A) and 54 CK-g-Eq (method B), and in group B 73 CK-g-Eq (method A) and 63 CK-g-Eq (method B). Mean values in group A₁ were lower than in group A₂ and group B (p < 0.05). It is concluded that MI size was significantly reduced to about one third after early reperfusion as compared with no reperfusion. In contrast, MI size was not significantly reduced after late reperfusion.     

Differential effects of sotalol and metoprolol on induction of paroxysmal supraventricular tachycardia

Seventeen patients with recurrent paroxysmal supraventricular tachycardia (SVT) underwent serial electrophysiologic studies to compare the effects of i.v. sotalol (1.5 mg/kg) and i.v. metoprolol (0.15 mg/kg). The plasma concentrations of sotalol (2.1 ±1.1 μg/ml) and metoprolol (67 ± 15 ng/ml) were within the therapeutic range. Before drug administration, sustained SVT could be reproducibly induced in all patients. Sotalol prevented induction of sustained SVT in 10 of 17 patients (59%) and metoprolol in 4 (28%) (p < 0.05). In 6 of 8 patients with atrioventricular (AV) nodal reentrance, the site of action of sotalol was the anterograde or the retrograde limb, reflecting an increase in refractoriness in both pathways of the circus movement. In 4 of 9 patients with AV reentrance, the site of action of sotalol was exclusively the AV nodal pathway; conduction through the extranodal accessory tract appeared to be unchanged, but lts anterograde effective refractory period was prolonged (from 285 ± 25 to 322 ± 28 ms, p <0.001; mean ± Standarddeviation). In the 7 patients in whom sotalol did not prevent sustained SVT, the tachycardia cycle length increased from 347 ± 42 to 392 ± 45 ms (p <0.01). Compared with sotalol, metoprolol had qualitatively similar but quantitatively less potent effects on the AV nodal pathways; however, different from sotalol, metoprolol had no effect on extranodal accessory tracts.The study suggests that at therapeutic plasma concentrations, sotalol would be effective in preventing clinical SVT in a significant proportion of patients refractory to metoprolol; because sotalol not only has β-blocking properties but also results in acute prolongation of the action potential duration, this combination of class II and III activity may contribute to its superior prophylactic efficacy compared with pure β blockade.     

Thrombolysis in acute myocardial infarction: effect of intravenous followed by intracoronary streptokinase application on estimates of infarct size

The effect of pretreatment with intravenous infusion of streptokinase (SK) (16,700 U/min for 90 minutes), started after diagnosis and followed by intracoronary application (2000 U/min) (protocol 1), was assessed retrospectively in 55 consecutive patients with acute transmural myocardial infarction (MI). Another 46 patients with acute MI treated previously by intracoronary thrombolysis served as control subjects (protocol 2). Reperfusion at first coronary injection was observed after pretreatment in 25 patients (45%), but in no control patient (p less than 0.001). Fifteen patients with successful pretreatment (group A), 20 patients with successful treatment according to protocol 2 (group B) and 9 patients with unsuccessful thrombolysis (group C) were restudied after 4 weeks. Data from patients with reinfarction, coronary bypass surgery or percutaneous transluminal coronary angioplasty before restudy were excluded. Thallium-201 scintigraphy was performed before and 24 hours after treatment, serum creatine kinase activity was measured every 8 hours for 3 days and regional ejection fraction (EF) of acute MI was determined before and 4 weeks after treatment. The scintigraphic, enzymatic and hemodynamic data before treatment indicated severe and comparable ischemia among the 3 groups. The thallium-201 perfusion defect decreased in group A (from 41 to 21%, p less than 0.01) and in group B (from 38 to 26%, p less than 0.01), but did not change in group C (from 37 to 31%, difference not significant). Peak serum creatine kinase levels normalized by the perfusion area of acute MI was 20, 33 and 58 U/liter unit in groups A, B and C. The mean values of groups A and C were significantly different (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracoronary thrombolysis in acute myocardial infarction: Correlations among serum enzyme,scintigraphic and hemodynamic findings

The effect of early reperfusion after intracoronary infusion of streptokinase in patients with acute myocardial infarction was assessed in 27 patients by serial analysis of serum creatine kinase (CK) activity, thallium-201 scintigraphy (seven pinhole technique) and left ventricular and coronary angiography. Serial serum CK activity determinations were carried out at hourly intervals. Thallium-201 tomographic scintigrams were obtained before and 24 hours after recanalization. The size of the perfusion defect was measured from eight scintigraphic cross sections of the left ventricle. Regional ejection fraction was determined from the left ventricular angiogram before and 4 weeks after recanalization. The results in three groups of patients are presented: group A, 10 patients with successful recanalization and a peak serum CK activity of less than 1,000 U/liter; group B, 9 patients with successful recanalization and a peak serum CK activity of more than 1,000 U/liter and group C, 8 patients with unsuccessful recanalization. Patients in group A showed an increase in CK activity (from 46 to 603 U/liter p < 0.001), a reduction in the thallium perfusion defect (from 115 to 49 °, p < 0.01) and an augmentation of regional ejection fraction (from 24 to 38 percent, p < 0.05). Patients in group B had an increase in serum CK activity (from 46 to 1,562 U/liter, p < 0.001), only a moderate reduction in the thallium perfusion defect (from 141 to 87 °, p < 0.01) and no change in regional ejection fraction (from 25 to 27 percent, p > 0.05). Patients in group C had an increase in serum CK activity (from 43 to 1,756 U/liter, p < 0.001), no change in the thallium perfusion defect (from 145 to 147 °, p > 0.05) and no change in regional ejection fraction (from 32 to 26 percent, p >0.05). Compared with patients in group B, those in group A had a shorter duration of ischemia (3.9 versus 4.8 hours), more frequently adequate collateral supply to the infarcting area before recanalization (40 versus 0 percent of patients) and a smaller area supplied by the occluded vessel (115 versus 141 °). Although all differences were not at the level of significance (p > 0.05), conditions for tolerating ischemia were better in group A than in group B.The study shows that early reperfusion has a beneficial effect on the extent of myocardial necrosis as estimated from serum enzyme determinations, thallium-201 scintigraphy and contrast ventriculography. The beneficial effect depends on the duration of myocardial ischemia and on the blood supply to the ischemic area by collateral vessels.     

Influence of diet on high-density lipoproteins

Evidence of a relation between diet and high-density lipoprotein (HDL) levels in humans comes from numerous cross-sectional and experimental studies. Evaluation of data from cross-sectional nutrition and health surveys sometimes yields different results for men and women but usually demonstrates positive correlations of HDL cholesterol levels with total energy intake, alcohol consumption, dietary cholesterol and total and animal fat, and negative correlations of HDL with dietary carbohydrates (simple sugars) and, in some instances, plant fats. Short-term dietary manipulation produced confirmatory evidence of a causal relation between diet and HDL with regard to several of these factors; however, there are few long-term data. The underlying mechanisms as well as the relation of HDL manipulation to cardiovascular health are still to be defined, particularly because the functions and fates of the HDL molecule may vary according to its composition and turnover, which are not reflected by the HDL cholesterol concentration. Furthermore, some relations between diet and HDL may only be the result of other metabolic consequences of dietary change, for instance, triglyceride metabolism and other lipoproteins. Although there is consistent evidence that a high HDL cholesterol level is indicative of a low risk of coronary heart disease in industrialized populations, evidence is inconclusive that manipulation of HDL leads to an alteration of risk.     

Diagnostic relevance of humoral and cytotoxic immune reactions in primary and secondary dilated cardiomyopathy

Circulating muscle-specific antimyolemmal antibodies (AMLAs) were found in 18 of 61 patients with secondary dilated cardiomyopathy (DC). All 18 patients had clinical or histologic evidence of previous perimyocarditis. AMLAs were found both in patients' serum samples and bound to the sarcolemmal sheath of the autologous myocardial biopsy specimen. Only AMLAs in postmyocardiac DC induced cytolysis of vital cardiocytes in the presence of complement, whereas hepatocytes remained unaffected. Titers of AMLAs correlated with the degree of cardiocytolysis. In contrast, antiinterfibrillary antibodies were found in 49 % patients with primary DC (n = 79) and in 61 % of patients (n = 30) with alcoholic DC. The incidence of antifibrillary antibodies of the antimyosin type was 23 and 24%, respectively. Incidence of both antibodies increased according to the severity assessed by New York Heart Association functional classes. Circulating immune complexes assayed by a new Clq-solid phase fluorometric assay were present in 30% of patients with postmyocarditic DC only. Lymphocyte-mediated cytotoxicity against heterologous cardiac target cells (K-cell activity) was measured in 33% of patients each with primary and secondary alcoholic DC but not postmyocarditic DC. There were no blocking factors in primary but were some in alcoholic heart disease.     

Diagnosis of increased pulmonary blood flow by suprasternal M-mode echocardiography in atrial septal defect

The right pulmonary artery (PA) was quantitatively assessed by Suprasternal M-mode echocardiography in 25 patients in whom an atrial septal defect (ASD) was suspected clinically. In 10 patients an ASD was excluded (Group 1) and in 15 it was confirmed (Group 2). The smallest diameter of the right PA at end-diastole in Group 1 was 8.8 ± 1.5 mm/m² body surface area and in Group 2 14.8 ± 3.6 mm/m² (p < 0.001). The greatest diameter of the right PA during systole was also much smaller in Group 1 (11.3 ± 1.2 mm/m²) than in Group 2 (17.7 ± 3.5 mm/m²) (p < 0.001). The absolute and percent systolic expansion of the right PA did not differ in the 2 groups (2.7 ± 0.5 mm [29.1 ± 10.8%] in Group 1 and 2.9 ± 0.8 mm [20.8 ± 9.8%] in Group 2). No correlation was found between measured and derived echocardiographic variables of the right PA and the magnitude of the left-to-right shunt. Patients in Group 2, who had an additional pressure elevation in the PA, showed, on average, a larger right PA and a smaller percent systolic expansion. The study demonstrates characteristic alterations in the wall motion pattern of the right PA in patients with ASD, indicating increased pulmonary blood flow.     

Secondary type II hyperlipoproteinemia in patients with anorexia nervosa.

In 18 patients with anorexia nervosa, plasma cholesterol and triglyceride concentral concentrations were repeatedly determined over a period of 14 mo. In 11 patients elevated cholesterol concentrations were found which were due to an increase of low-density lipoprotein cholesterol, whereas high-density lipoprotein and very low density lipoprotein cholesterol levels were in the normal range. The elevated cholesterol values did not correlate with clinical and laboratory parameters such as the degree of weight loss and thyroid function tests. In follow-up studies it could be shown that in patients who regained their original weight, elevated plasma cholesterol concentrations fell to normal levels parallel to weight increase. In patients who showed no change in weight, however, cholesterol levels remained high. The cause for this secondary type II hyperlipoproteinemia in anorexia nervosa is not known. Hepatic triglyceride lipase and lipoprotein lipase activities in post-heparin plasma were found to be low despite normal triglyceride concentrations.     

Ventricular arrhythmias late after aortic valve replacement and their relation to left ventricular performance

Sudden unexplained death is a common cause of late mortality after aortic valve replacement. To evaluate the occurrence of ventricular arrhythmia in patients with aortic valve replacement, two 24 hour ambulatory electrocardiographic recordings were obtained in 45 such patients (mean age 55 years) who had undergone replacement an average of 3.3 years previously. In 43 patients, ventricular arrhythmia was detected; it was rare (mean premature ventricular complex frequency less than $\text{1}\text{15}$ min) in 18 patients (40 percent), moderately frequent (mean frequency $\text{1?}\text{10}\text{15}$ min) in 14 patients (31 percent) and frequent (mean frequency more than $\text{10}\text{15}$ min) in 11 patients (24 percent). Multiformity was noted in 40 (89 percent), bigeminy in 27 (60 percent), couplets in 27 (60 percent) and ventricular tachycardia in 16 (36 percent) of the 45 patients studied. The occurrence of ventricular arrhythmia was not related to the predominant hemodynamic lesion or to the presence of coronary artery disease as determined at the time of preoperative cardiac catheterization. Radionuclide left ventricular ejection fraction, determined at the time of electrocardiographic monitoring in 39 patients, demonstrated normal left ventricular function (ejection fraction greater than 50 percent) in 27 patients (60 percent), moderately depressed function (ejection fraction 36 to 50 percent) in 8 (21 percent) and severe dysfunction in 4 (10 percent). When patients with abnormal versus normal left ventricular performance were compared, the mean premature ventricular complex frequency was $\text{21 ±}\text{26}\text{15}\text{min}\text{versus}\text{5 ±}\text{11}\text{15}\text{min (}\text{p}\text{< 0.01)}$; couplets occurred in 10 (83 percent) of 12 versus 13 (48 percent) of 27 patients (p < 0.05) and ventricular tachycardia in 8 (75 percent) of 12 versus 6 (22 percent) of 27 patients (p < 0.01). Patients exhibiting ventricular tachycardia had a mean left ventricular ejection fraction of 47 ± 14 percent compared with 62 ± 13 percent in patients without this arrhythmia (p < 0.005). This study indicates that significant ventricular arrhythmias, including ventricular tachycardia, are common late after aortic valve replacement. In addition, a relation exists between occurrence of arrhythmia and left ventricular function abnormalities.     

Atrioventricular dissociation detected by suprasternal M-mode echocardiography: a clue to the diagnosis of ventricular tachycardia

Twenty-two patients were studied by suprasternal M-mode echocardiography during ventricular tachycardia (VT). Adequate echocardiograms were obtained from 19 patients. Thirteen patients showed atrioventricular (AV) dissociation and 6 patients a ventriculoatrial contraction pattern according to the left atrial (LA) contraction obtained from the suprasternal notch. In 1 of these 6 patients, a 2:1 block retrograde was found by echocardiography. In another patient, an intermittent block occurred in the retrograde direction. In 4 patients, a constant relation between the QRS complex and LA contraction soon after the beginning of the QRS complex was seen, demonstrating a 1:1 ventriculoatrial conduction. According to the LA contraction obtained from the suprasternal echocardiogram, 13 patients showed AV dissociation and 6 patients a retrograde conduction to the LA. From the analysis of the 12-lead standard electrocardiogram obtained simultaneously during VT, AV dissociation could be recognized in only 3 patients. Thus, AV dissociation during VT is more easily diagnosed with suprasternal M-mode echocardiography than with the standard electrocardiogram.     

Coronary collateral vessels: Their significance for left ventricular histologic structure

Whether coronary collateral vessels protect the left ventricular myocardium is unknown. Light microscopic morphometry was carried out on myocardial tissue samples from 56 surgically treated patients with coronary artery disease. Transmural biopsy of the myocardium perfused by the left anterior descending coronary artery was obtained during open heart surgery. In initial reproducibility studies of biopsy samples of 17 patients a sampling error for evaluation of myocardium was defined and differences in transmural fibrosis exceeding ±6.2 percent were considered biologically significant. Stenosis of the left anterior descending artery was determined from preoperative angiography. Group A (control group) comprised patients with less than 75 percent area reduction of the left anterior descending coronary artery (mean ± standard deviation 65 ±10 percent). Patients in group B (more than 95 percent area reduction [mean 99 ± 2 percent] without collateral supply on arteriography) were compared with patients in group C (identical stenosis [mean 99 ± 2 percent] but with collateral supply). Fibrosis averaged 17 percent in group A, 68 percent in group B (p < 0.001 versus group A) and 29 percent in group C (p > 0.05 versus group A, p < 0.001 versus group B). Thus, in severe coronary stenosis myocardium supplied by collateral vessels shows less fibrosis on biopsy sample than does myocardium without collateral supply.     

Dissociation between in vivo and in vitro measurements of converting enzyme activity after chronic oral treatment with captopril in rats

Intravenous administration of captopril (20 micrograms) produced inhibition of angiontensin I pressor responses by 70 percent and of plasma-converting enzyme activity by 72 percent. Oral treatment with captopril (50 mg/kg/day) for 1 week inhibited angiotensin I pressor responses more (84 percent) than plasma-converting enzyme activity (23 percent). Four month oral treatment of normotensive and spontaneously hypertensive rats with captopril (50 mg/kg/day) led to 68 and 71 percent inhibition of angiotensin I pressor responses, but produced increases in plasma-converting enzyme activity of 123 and 94 percent, respectively. In spontaneously hypertensive rats, elevated converting enzyme activity in the medulla oblongata was measured after this treatment. It is concluded that plasma-converting enzyme activity measurements can be dissociated from the in vivo inhibition of converting enzyme. Chronic oral captopril treatment results in an induction of converting enzyme biosynthesis not only in peripheral tissue but also in the brain.     

Estimation of left ventricular myocardial function by the ejection fraction in isolated, chronic, pure aortic regurgitation

In patients with aortic regurgitation (AR), the left ventricular (LV) ejection fraction (EF) may not adequately reflect depressions of myocardial contractility due to decreased aortic impedance. The sensitivity of end-systolic pressure-volume relations and stress-volume relations in detecting myocardial depression in patients with AR was studied. In 12 patients with normal valvular function but with varying LV function (due to coronary heart disease in 9 patients and dilated cardiomyopathy in 3 patients) (group 1), and in 8 patients with AR (group 2), LV angiography was performed before and after sublingual application of isosorbide dinitrate. Heart rate was kept constant by right atrial pacing. In group 1, the slope k of the end-systolic pressure-volume relation was to EF at rest: k = 0.091.e0.051 EF; r = 0.88. In AR, this relation was shifted significantly to the right: k = 0.019.e0.066 EF; r = 0.92. This shift persisted when the end-systolic stress-volume relation instead of the end-systolic pressure-volume relation was calculated. Thus, in patients with AR the end-systolic pressure-volume relation is flatter than that in patients with intact valvular function at a given EF. The same is true for the end-systolic stress-volume relation. The data indicate that EF overestimates myocardial contractility in AR compared with end-systolic pressure-volume or stress-volume relations. This overestimation is probably a result of decreased aortic impedance in AR.