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Biomedical subjects

W Kübler

Publications and source records attributed to W Kübler.

At least 19 recordsLinked to original sources
PubMed1992

Decreased concentration of myofibrils and myofiber hypertrophy are structural determinants of impaired left ventricular function in patients with chronic heart diseases: a multiple logistic regression analysis.

OBJECTIVES: The aim of this study was to perform a multiple logistic regression analysis to identify independent structural determinants of impaired left ventricular function. BACKGROUND: The association between contractile failure and structural alterations of the myocardium has been demonstrated in several studies, and multiple interactions between myocardial structure and cardiac performance are likely. METHODS: Morphometric data assessed from 130 left ventricular biopsy specimens were analyzed. The endomyocardial specimens were obtained from 57 patients with normal coronary arteries (17 with normal left ventricular ejection fraction and 40 with impaired left ventricular function [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32 patients with aortic valve disease. Transmural biopsy specimens were assessed in 6 donor hearts before heart transplantation and in 20 patients with left anterior descending coronary artery disease whose specimens were obtained from the left ventricular anterior wall during aortocoronary bypass surgery. Global or regional left ventricular function was evaluated from left cineventriculograms. The volume fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils, volume fraction of myofibrils related to myocardial tissue (including fibrosis) and myofiber diameters were determined from semithin sections of the biopsy specimens with the use of light microscopic morphometry. RESULTS: Multiple logistic regression analysis revealed decreased volume fraction of myofibrils (p < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of impaired left ventricular function. CONCLUSIONS: These data indicate that, independent of the underlying heart disease, both decreased concentration of contractile proteins and myocyte hypertrophy are independently associated with impaired left ventricular function.

Age Factors↗
PubMed1992

Greater diagnostic sensitivity of treadmill versus cycle exercise testing of asymptomatic men with coronary artery disease.

Maximal hemodynamic and ventilatory responses using cycle and treadmill ergometer were compared in 52 asymptomatic patients with angiographically proved coronary artery disease. Moreover, test sensitivity with respect to ST-segment depression and typical angina pectoris were compared between exercise modes used. Exercise tests were performed on different days in randomized order. In 42 patients, exercise-induced myocardial ischemia, expressed as a fraction of left ventricular circumference, was assessed by thallium-201 scintigraphy. The main finding of this study was a significantly higher maximal oxygen uptake (1.87 +/- 0.4 vs 2.2 +/- 0.5 liters/min; p less than 0.001), heart rate (148 +/- 19 vs 158 +/- 18 beats/min; p less than 0.001) and rate-pressure product (28.3 +/- 5 x 10(3) vs 30.7 +/- 5 x 10(3); p less than 0.001) during treadmill walking than during cycling. Therefore, stress-induced myocardial ischemia was significantly more extensive after treadmill walking (31 +/- 37 degrees vs 45 +/- 40 degrees; p less than 0.001). Moreover, there were significantly more patients with signs of myocardial ischemia (ST-segment depression or typical angina pectoris, or both) during treadmill than during cycle ergometry (35 vs 25 patients; p less than 0.05). However, lactate levels measured at peak exercise (4.07 +/- 2.0 vs 4.38 +/- 1.9 mmol/liter) and 3 minutes into the recovery period (5.60 +/- 2.2 vs 5.80 +/- 2.2 mmol/liter) were comparable between both methods, indicating no significant difference in anaerobic energy production. These findings suggest that walking on a treadmill represents an exercise method with a greater ability than cycling to detect coronary artery disease.

Coronary Disease↗
PubMed1992

Baroreceptor-mediated release of vasopressin in patients with chronic congestive heart failure and defective sympathetic responsiveness.

In patients with congestive heart failure (CHF), overactivity of the sympathetic nervous system may be accompanied by an impairment of the baroreflex control mechanism. To evaluate the reflex responses of the sympathetic nervous system, the renin-angiotensin system and vasopressin release to baroreceptor unloading, 38 patients with left ventricular dysfunction were studied. Hemodynamic data, and plasma norepinephrine, renin activity and vasopressin concentrations were measured before and 60 minutes after administration of high-dose hydralazine (0.4 mg/kg intravenously). On the basis of blood pressure response to vasodilator administration, patients were divided arbitrarily into those with a decrease in mean arterial blood pressure greater than or equal to 15 mm Hg (group A; n = 12) and those with a decrease less than 15 mm Hg (group B; n = 26) compared with control values. In response to hydralazine, heart rate decreased in group A from 100 to 92 beats/min (p less than 0.001) and increased in group B from 90 to 96 beats/min (p less than 0.05). In group A, hemodynamic changes induced by hydralazine were accompanied by a decrease in plasma norepinephrine from 822 to 518 pg/ml (p less than 0.01) and an increase in plasma vasopressin from 8.4 to 45.2 pg/ml (p less than 0.001). In group B, plasma norepinephrine and vasopressin did not change significantly (407 vs 447, and 8.4 vs 8.3 pg/ml, respectively). Plasma renin activity remained unchanged in group A and increased in group B (p less than 0.001). The data show that baroreceptor-mediated release of vasopressin is not impaired in patients with CHF and a defective sympathetic reflex control mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Comparison of captopril with enalapril in the treatment of heart failure: influence on hemodynamics and measures of renal function.

Twenty-nine patients with severe heart failure (NYHA III) were randomly assigned to receive therapy with an angiotensin converting enzyme inhibitor (ACE inhibitor), either captopril or enalapril. The mean daily dosage of captopril was 56 +/- 5 mg and of enalapril 9.5 +/- 0.4 mg. After a mean of 8 +/- 1 days, the influence of both ACE inhibitors on hemodynamics and renal function was compared. The mean arterial pressure in the group treated with captopril (Group A) fell by 9 +/- 3 mmHg (p less than 0.01), and in the group treated with enalapril (Group B) it fell by 12 +/- 3 mmHg (p less than 0.001). The difference between the groups was not significant. Heart rate decreased in both groups; however, the change was significant (p less than 0.05) only in patients treated with enalapril (-11 +/- 3 bpm in Group B vs. -7 +/- 4 bpm in Group A). Stroke volume index increased by 6 +/- 3 ml/m2 in Group A (p less than 0.05) vs. 10 +/- 2 ml/m2 in Group B (p less than 0.01). The increase in stroke volume index was not significantly different between the two groups. Mean decreases in pulmonary artery and right atrial pressure were also comparable in both groups. Thus, hemodynamic improvements were similar during therapy with either captopril or enalapril. Serum sodium and potassium before therapy were 137 +/- 1 mmol/l and 4.1 +/- 0.1 mmol/l, respectively, in group A and 139 +/- 1 mmol/l and 4.0 +/- 0.1 mmol/l, respectively, in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1992

Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study.

To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual-isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for 201Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r = 0.75, p < 0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses > or = 75% (IP-PA: 70.0%, 201Tl: 66.3%, P = NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P = 0.021), suggesting that visual analysis of serial IPPA scintigrams may overestimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% +/- 11% vs 44% +/- 11% in normal myocardium, P < 0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with 201Tl for the detection of stress-induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability.

Algorithms↗
PubMed1992

Myocardial perfusion and regression of coronary artery disease in patients on a regimen of intensive physical exercise and low fat diet.

This intervention program tested the applicability and effects of intensive physical exercise and a low fat diet on progression of coronary atherosclerotic lesions and stress-induced myocardial ischemia in patients with stable angina pectoris. Eighteen patients participated in this program for 1 year; they consumed a low fat, low cholesterol diet (less than 20 energy % fat, cholesterol less than 200 mg/day) and exercised for greater than 3 h/week. Change in coronary morphology was assessed by angiography and digital image processing; stress-induced myocardial ischemia was measured by thallium-201 scintigraphy. Results were compared with those in patients receiving "usual care." In the intervention group, significant regression of coronary atherosclerotic lesions was noted in 7 of the 18 patients; no change or progression was present in 11 patients. In patients receiving usual care, regression was detected in only 1, with no change or progression in 11 patients (different from intervention, p less than 0.05). There was a significant reduction in stress-induced myocardial ischemia, which was not limited to patients with regression of coronary atherosclerotic lesions. Thus, regular physical exercise and a low fat diet may retard progression of coronary artery disease; however, improvement of myocardial perfusion may be achieved independently from regression of stenotic lesions.

Angiography, Digital Subtraction↗
PubMed1992

Reduction of myocardial ischemia by gallopamil: a dual-isotope study with thallium-201 and iodine-123 phenylpentadecanoic acid.

The present study was performed for characterizing the effect of chronic oral treatment with the calcium antagonist gallopamil on regional myocardial perfusion and free fatty acid utilization in poststenotic human myocardium. Twenty-two patients with angiographically documented coronary artery disease and stable angina pectoris underwent consecutive dual-isotope studies following simultaneous injection of 80 MBq thallium-201 and 200 MBq iodine-123 phenylpentadecanoic acid (IPPA) during a symptom-limited stress test. Radionuclide studies were performed after 1 week of placebo treatment (baseline), 4 weeks after oral treatment with 50 mg of gallopamil t.i.d. and again after 1 week of double-blind treatment with gallopamil or placebo. As compared to baseline, initial (poststress) uptake of both tracers in poststenotic myocardial segments was significantly improved after 4 weeks of treatment with gallopamil [thallium-201, +9.0%; p < 0.001; 95% confidence interval (CI), 4.3-13.6%; IPPA, +11.8%; p = 0.003; 95% CI, 4.2-19.3%]. Poststenotic IPPA-clearance was likewise significantly increased (+28.2%; p < 0.001; 95% CI, 12.4-44.0%) indicating a considerably enhanced myocardial fatty acid oxidation after treatment. In the final double-blind phase, myocardial uptake of both tracers as well as IPPA clearance remained enhanced in the subgroup of patients receiving gallopamil and returned to baseline values in patients receiving placebo. Thus, in poststenotic myocardium, chronic treatment with gallopamil provokes an improvement of both regional myocardial perfusion (as demonstrated by an increased tracer uptake in poststress scintigrams) and regional myocardial fatty acid utilization (as demonstrated by an increased uptake and clearance of IPPA).

Algorithms↗
PubMed1992

Sotalol exhibits reverse use-dependent action on monophasic action potentials in normal but not in infarcted canine ventricular myocardium.

In 12 anesthetized mongrel dogs (30 mg/kg pentobarbital), a thoracotomy was performed, and the left anterior descending coronary artery was ligated proximally. Eight to 12 days later, monophasic action potentials were recorded endocardially from the apex of the noninfarcted right ventricle and infarcted areas of the left ventricle, and the effects of 1.5 mg/kg intravenous sotalol were evaluated. Monophasic action potentials from the infarcted zone of the left ventricle were obtained from areas where fractionated bipolar electrograms could be recorded; this was histologically confirmed. After sotalol, in sinus rhythm, the monophasic action potential duration at 90% repolarization of the infarcted zone increased from 186 +/- 31 to 226 +/- 45 ms (+ 22%, p less than 0.05), and monophasic action potential duration of the noninfarcted zone increased from 184 +/- 31 to 225 +/- 47 ms (+ 22%, p less than 0.05). Programmed ventricular stimulation was performed with single extrastimuli at a basic drive cycle length of 300 ms. With long coupling intervals (290 ms), monophasic action potential duration of the infarcted zone increased from 165 +/- 23 to 183 +/- 25 ms (+ 11%, p less than 0.05) after sotalol; and monophasic action potential duration of the noninfarcted zone increased from 159 +/- 20 to 180 +/- 25 ms (+ 13%, p less than 0.05). With short coupling intervals (200 ms), the monophasic action potential duration of the noninfarcted zone increased from 157 +/- 19 to 173 +/- 18 ms (+ 10%, p less than 0.05), and monophasic action potential duration of the noninfarcted zone increased from 150 +/- 18 to 157 +/- 18 ms (+ 5%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1992

Differential effects of quinidine on transmembrane action potentials of normal and infarcted canine Purkinje fibers.

Fourteen days after proximal ligation of the left anterior descending coronary artery (LAD) of mongrel dogs, the effects of quinidine on action potentials of normal and infarcted Purkinje fibers were evaluated. The concentration-dependent (10(-7)-3 x 10(-5) M) and frequency-dependent (1 and 3 Hz) actions of quinidine were evaluated by the following parameters: maximum upstroke velocity (Vmax), action potential duration at 50 and 95% repolarization (APD50, APD95), effective refractory period (ERP), resting membrane potential (RMP), and action potential amplitude (APA). Quinidine reduced Vmax in normal and abnormal Purkinje fibers in a concentration- and frequency-dependent manner; these effects were more pronounced in infarcted tissue. The APD50 was shortened significantly at 1 Hz in noninfarcted Purkinje fibers, whereas in infarcted Purkinje fibers quinidine had no effect on APD50. The APD95 was not significantly altered by quinidine in normal Purkinje fibers; in infarcted areas APD95 was significantly prolonged at 1 and 3 Hz. The effective refractory period (ERP) was prolonged in normal and infarcted Purkinje fibers, these effects were more marked in ischemically damaged fibers. No effects were observed on resting membrane potential (RMP). APA was reduced significantly after quinidine at 1 and 3 Hz; there was no difference between normal and infarcted tissue. These data indicate a differential effect of quinidine in normal and infarcted Purkinje fibers which may be an important mechanism of action of quinidine in infarcted tissue.

Action Potentials↗
PubMed1992

Cardiac sympathetic nervous activity during myocardial ischemia, reperfusion and ventricular fibrillation in the dog--effects of intravenous lidocaine.

In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after occlusion of the left anterior descending coronary artery as well as during reperfusion and ventricular fibrillation (VF). In 7 control animals, CSNA did not significantly differ from preocclusion levels when determined 20 min after occlusion (+3.5 +/- 1.5%, mean +/- SEM) and up to 15 min following reperfusion (+1.5 +/- 0.6%). However, VF was associated with a potential increase in CSNA by 106 +/- 15.5% (p less than 0.001). The effect of lidocaine (6 mg/kg) on cardiac sympathetic tone was examined in 5 additional animals. Lidocaine reduced control CSNA by 23 +/- 4.7% (p less than 0.001); subsequent ischemia and reperfusion did not substantially change the level of preocclusion activity. CSNA decreased significantly also during VF (52 +/- 4.2%, p less than 0.001). In conclusion, efferent CSNA was slightly altered in the course of acute myocardial ischemia and reperfusion, but significantly increased during VF. Lidocaine produced marked attenuation of CSNA in anesthetized dogs.

Animals↗
PubMed1992

Electrophysiologic and antiarrhythmic effects of D-sotalol.

There is extensive experimental and clinical experience concerning the antiarrhythmic potency of DL-sotalol, a beta-adrenergic antagonist that lengthens the cardiac action potential duration. More recently, its dextrorotatory isomer, D-sotalol, has been evaluated in experimental studies and preliminary clinical trials. Whereas the isomer is almost free of beta-blocking activity, both experimental and clinical data demonstrate that potent class III activity of D-sotalol. Further investigations, particularly in patients with life-threatening arrhythmias, are needed to delineate the clinical usefulness of this compound.

Action Potentials↗
PubMed1992

Effect of gallopamil on neutrophil function: experimental and clinical studies.

The purpose of the study was to investigate whether gallopamil interferes with neutrophil activation. In vitro, gallopamil caused a dose-dependent reduction in phorbol myristate acetate-stimulated superoxide anion production by neutrophils as measured by the superoxide dismutase inhibited reduction of cytochrome C [concentration of 50% inhibition (IC50) = 9.5 x 10(-6) mol/L]. Furthermore, gallopamil reduced the platelet-activating factor-induced loss of neutrophil deformation, which was assessed by filtrometry (IC50 = 4.3 x 10(-6) mol/L). The effect of gallopamil was assessed in 24 patients during elective balloon angioplasty. Gallopamil (0.4 mg) or placebo (double-blind conditions) was administered by intracoronary application during the 10-min interval between the first two balloon inflations. In the placebo group, blood samples obtained simultaneously from the coronary sinus and from the femoral artery revealed an increase in the proportion of activated neutrophils in the coronary sinus blood after the second balloon inflation [nitro blue tetrazolium (NBT) score, NBT test: 15 +/- 9% relative coronary sinus and arterial blood difference, p < 0.05]; these changes in NBT score were similar to those after the first balloon inflation. In the gallopamil-treated group, however, significant arterial and coronary sinus blood differences in NBT scores were not found after the second balloon inflation. Gallopamil may, thus, attenuate the local neutrophil activation during balloon angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1992

Intracoronary gallopamil during percutaneous transluminal coronary angioplasty.

The present study was designed to investigate the effect of the calcium-channel antagonist gallopamil on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA). Twenty-four adult patients with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) were randomly assigned to receive gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralization of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease, or renal failure were excluded from the study. PTCA was performed with use of at least two balloon inflations, each of 2 min in duration. Gallopamil (0.4 mg) or placebo (0.9% sodium chloride) was administered during the 10-min interval between the two inflations. For determination of myocardial lactate and hypoxanthine release, blood samples were taken simultaneously from the great cardiac vein and the femoral artery before and immediately after each inflation. Electrocardiogram changes were analyzed by measuring ST-segment deviations (80 ms after the J point) and maximal T-wave deviations of the leads I, II, III, and V2, V4, and V6. The most sensitive leads for identification of myocardial ischemia in the LAD area were V2 and V4. If compared to the first balloon inflation, the degree of ST-segment/T-wave changes induced by the second inflation was significantly reduced only in the presence of gallopamil. Furthermore, if compared to placebo, ischemia-induced lactate and hypoxanthine release was decreased in the presence of gallopamil. These results suggest that intracoronary application of gallopamil attenuates myocardial ischemia during PTCA.

Adult↗