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H R Figulla

Publications and source records attributed to H R Figulla.

At least 145 records · Page 8Linked to original sources

Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy.

The defects underlying the impairment of systolic pump function in human dilated cardiomyopathy (DCM) are not known. We isolated mitochondrial particles from 10 hearts of transplant recipients with DCM and from nine normal hearts not used for transplantation. Yield was similar in both groups (2.77 vs 2.81 mg mitochondrial protein per gram heart). Cytochrome content (difference spectrophotometry) was found reduced in DCM mitochondria, e.g. cytochrome c was 0.295 +/- 0.06 in the DCM group and 0.371 +/- 0.04 mumol g-1 in the control group (P less than 0.05). Enzymatic activity of the cytochrome-containing complexes III (3.77 +/- 0.82 vs 4.95 +/- 1.15 mumol min-1.mg-1) and IV (2.63 +/- 0.96 vs 3.65 +/- 0.6 mumol min-1.mg-1) of the respiratory chain was reduced in the DCM group (P less than 0.05). Complex IV, the cytochrome c oxidase, in the DCM group showed impaired activity also in whole heart homogenates (0.173 +/- 0.04 vs 0.258 +/- 0.8 mumol min-1.mg-1). Subunit composition of the cytochrome c oxidase on sodium dodecyl sulphate-gel electrophoresis did not differ between DCM and normal hearts. Activity of complexes II and V of the respiratory chain, not containing cytochromes, was unchanged in DCM mitochondria compared with the control group. The present data show a decrease in cytochrome content and in cytochrome-dependent enzyme activity in human dilated cardiomyopathy. Further studies are necessary to clarify whether these findings are specific for dilated cardiomyopathy or whether they are epiphenomena of failing hearts.

Apyrase↗

Arguments supporting the use of calcium antagonists in idiopathic dilated cardiomyopathy: theoretical considerations and clinical results.

There is increasing evidence that sarcolemmal disorders in idiopathic dilated cardiomyopathy (IDC), due either to viral infection, catecholamine excess, ethanol intoxication, microcirculatory disorders, or autoimmune responses, induce enhanced Ca2+ inflow. This may lead to mitochondrial Ca2+ accumulation and activation of phospholipase and proteases, resulting in left ventricular dysfunction. The acute beneficial hemodynamic response to diltiazem in IDC patients, in comparison to other calcium blockers, enabled us to perform an open trial investigating the effects of chronic diltiazem (60-90 mg t.i.d.) in patients with IDC. The results of this trial suggested that adjunctive diltiazem in IDC had beneficial effects on mortality, hemodynamics, and symptoms. Thus a multicenter, double-blind, placebo-controlled trial was initiated.

Calcium Channel Blockers↗

Beneficial effects of long-term diltiazem treatment in dilated cardiomyopathy.

There is increasing evidence that chronic enhanced exogenous or endogenous catecholamine stimulation in patients with dilated cardiomyopathy may worsen hemodynamic status and prognosis. The cause of this deterioration may lie in myocellular calcium accumulation and microcirculatory disorders. In a prospective study, the calcium channel antagonist diltiazem was given to 22 patients with dilated cardiomyopathy (60 to 90 mg three times daily) in addition to conventional therapy of digitalis, diuretics and vasodilators. Twenty-five patients received the conventional therapy and served as historical controls. Eight additional patients who were not originally included in this control group received adjunctive diltiazem treatment after initially receiving conventional therapy alone. The three patient groups were similar in all hemodynamic and anamnestic features. Only patients with reduced myofibrillar volume fraction on myocardial biopsy were included in the trial, because they could be expected to show hemodynamic deterioration. The mean survival time was 29 months in the control group, whereas no patient in the diltiazem group died over a mean follow-up period of 15.4 months (p less than 0.001). Mean left ventricular ejection fraction increased from 0.34 to 0.44 (p less than 0.001) and New York Heart Association functional class improved significantly in the diltiazem group and during the diltiazem period in the crossover patients, but deteriorated in the control group. The results suggest that adjunctive diltiazem treatment in dilated cardiomyopathy has beneficial effects on mortality, hemodynamics and symptoms.

Adult↗

Will emergency coronary bypass grafting after failed elective percutaneous transluminal coronary angioplasty prevent myocardial infarction?

An emergency aorto-coronary bypass grafting operation was performed within 12 hours after the development of acute myocardial ischemia due to partial or complete vascular occlusion in 34 of 950 (3.6%) patients who had received elective percutaneous transluminal coronary angioplasty (PTCA). Of the 34 patients, three (= 8.8%) died postoperatively in irreversible cardiogenic shock. Half of the surviving patients developed a Q-wave infarction after the operation, whereas the other half remained without transmural infarct. With comparable clinical data and times of operation up to placement of the aorto-coronary bypass vessel, an adequate residual perfusion must still have been present in the cases with non Q-wave infarction. Since in many cases a myocardial necrosis is unavoidable despite relatively early operative revascularization, the decisive role will be played by the remaining perfusion of the vessel concerned and any collaterals. It follows that treatment of an early PTCA complication, occurring in the catheter laboratory, ought to be the earliest possible aorto-coronary bypass operation unless available cardiological methods can reliably assure reperfusion. Treatment of a PTCA complication occurring later, however, e.g. after hours in the intensive-care unit, should be a repeat PTCA attempt: surgery at this stage will not prevent the transmural infarction but will increase risk of lethal complications.

Adult↗

[Beneficial long-term effects of diltiazem on the course of dilated cardiomyopathy].

There is increasing evidence that chronic enhanced exogenic or endogenic catecholamine stimulation in patients with dilated cardiomyopathy may worsen hemodynamics and prognosis. The cause of this may lie in myocellular calcium accumulation and microcirculatory disorders. In a prospective study the calcium antagonist diltiazem was given to 22 patients with dilated cardiomyopathy (60-90 mg t.i.d.) in addition to conventional therapy of digitalis, diuretics, and vasodilators. Twenty-five patients received the conventional therapy and served as historical controls. Eight additional patients who were not originally included in the 25 controls changed over from conventional therapy to adjunctive diltiazem treatment. The patient groups compared were similar in all hemodynamic and anamnestic features. Further, only patients with reduced myofibril volume fraction in the myocardial biopsy were included in the trial, since hemodynamic deterioration could be expected in them. The mean survival rate was 29 months in the controls, while within a mean of 15.4 months no patient died in the diltiazem group (p less than 0.001). Mean left ventricular ejection fraction increased from 0.34 to 0.44 (p less than 0.001) and the New York Heart Association classification was significantly improved in the diltiazem group and during the diltiazem period in the crossovers, but deteriorated in the controls. Therefore, the results suggest that adjunctive diltiazem treatment in dilated cardiomyopathy has beneficial effects on letality, hemodynamics, and symptoms.

Adult↗

[Excimer laser coronary angioplasty in high-grade stenoses and chronic occlusion].

Excimer-laser-angioplasty offers the advantage of minimal thermal injury to adjacent tissue compared to other laser ablation techniques. Highly flexible glass-fiber-catheter systems are now available, and are capable of transmitting sufficient energy densities to ablate even calcified atherosclerotic coronary plaques. We report initial results of excimer-laser-ablation of severe coronary stenoses and occlusions in 17 patients. An excimer-laser (308 nm) with a pulse duration of 50 ns and a repetition rate of 10 to 40 Hz served as laser source. Eight patients had a chronic total occlusion (RCA, n = 4, RCx, n = 3, LAD, n = 1), nine patients had 90% to 95% stenoses (LAD, n = 7, RCA, n = 2). In all cases a laser-catheter consisting of 17 circumferentially orientated 100 microns glass-fibers and a central 15/1000-inch lumen could be advanced to the stenoses/occlusion over a guidewire that had been passed across the stenoses/occlusion. Stenoses diameter could be reduced by 41.5 +/- 10.1% in all patients and vessel lumen was further increased by subsequent balloon dilatation in 10 cases. After 24 h, 16 vessels were patent and showed no restenoses; one recanalized RCA was found reoccluded. We observed no complications, such as perforation, spasm, or thrombi.

Aged↗

Occurrence and clinical significance of endocardial late potentials and fractionations in idiopathic dilated cardiomyopathy.

In order to assess the occurrence and clinical significance of abnormal electrograms in idiopathic dilated cardiomyopathy, endocardial electrode mapping during sinus rhythm and programmed ventricular stimulation were performed in 52 patients with or without clinical ventricular tachycardia. Abnormal endocardial electrograms were recorded in 77% of the patients and were diffusely distributed over the entire left ventricular endocardium. No relation could be established between the occurrence of late potentials or fractionations and clinical or induced arrhythmias. Endomyocardial biopsy samples were taken from 20 patients and showed that reduced myofibril volume fraction was related to the occurrence of abnormal endocardial electrograms. Neither induced arrhythmias nor the presence of late potentials or fractionations identified patients who died of sudden cardiac death during the mean (SD) follow up of 33 (11) months. Thus abnormal endocardial electrograms recorded during sinus rhythm in idiopathic dilated cardiomyopathy may only be interpreted as being a sign of damage to the myocardial cells.

Action Potentials↗

Inhomogenous capillary flow and its prevention by verapamil and hydralazine in the cardiomyopathic Syrian hamster.

There is clinical evidence that human dilated cardiomyopathy is related to microcirculatory disorders. We used an experimental preparation of the disease that consisted of a study of the microcirculation of 45 cardiomyopathic Syrian and 18 control hamsters with timed plasma staining. To investigate dynamic vascular disorders a double injection technique was used that permitted demonstration of all permanently and temporarily perfused capillaries in the same animal. The results showed a total capillary density of 3423 +/- 470 capillaries/mm2 in the cardiomyopathic hamster during the premyocytolic phase (30 days of age) and that of 3289 +/- 506 capillaries/mm2 during the myocytolytic phase (44 days). These values were not significantly different from those in the control group (3349 +/- 473 capillaries/mm2 at 30 days and 3383 +/- 556 capillaries/mm2 at 44 days). However, tissue areas with extended coronary transit times were detected only in the cardiomyopathic hamsters. These areas were of the same individual and cumulative size at 30 days (diameter approximately 200 micron, 4% of the tissue) as the myocytolytic zones at 44 days. In cardiomyopathic hamsters verapamil and hydralazine prevented both hypoperfusion and myocytolysis. The results favor the view that microcirculatory disorders generate tissue damage in the cardiomyopathic hamster and that these disorders can be prevented through treatment with the calcium antagonist verapamil or with the vasodilator hydralazine.

Animals↗

[Doppler echocardiography determination of the minute heart volume in ergometric stress].

To prove the use of Doppler-echocardiography in the determination of cardiac output during supine bicycle exercise, 14 patients suffering from dilatative cardiomyopathy were studied. Cardiac output was simultaneously determined by Doppler-echocardiography and with radionuclide ventriculography. In some cases, cardiac output was additionally measured using the thermodilution technique. In 12 patients (success rate 86%) flow velocity signals from the ascending aorta could be recorded with sufficient quality. Both methods were closely correlated, the r-value was 0.91 and the standard error of estimate was found to be 2.09 l/min. Mean deviation was 1.50 l/min (0.09-5.45 l/min) or 13% (1%-64%) respectively. For changes in cardiac output with exercise, the correlation was r = 0.88 with a mean deviation of 69% (2%-453%). The coefficient of variation for exercise measurements was 19% and did not differ from the resting value of 20%. Comparing the mean values of the whole group, no differences between the two methods could be found at rest, during exercise or for changes from rest to maximal exercise. Using the suprasternal approach, aortic flow velocities can be assessed by Doppler-echocardiography during exercise. Gross estimation of cardiac output during exercise seems possible; judgement of changes in cardiac output in individual cases appears to be uncertain.

Adult↗

[Clinical and hemodynamic effects of nisoldipine and captopril in heart failure: a double-blind comparative study of long and short-term effects].

Afterload reduction with angiotensin-converting enzyme inhibitors (ACE-inhibitors), such as captopril, is an established therapeutic measure in the adjunctive treatment of severe chronic heart failure. Unfortunately, several side effects and adverse reactions are related to this form of therapy. Calcium antagonists of the dihydropyridine group can also induce a similar afterload reduction, and substances of this group exhibit only a few adverse reactions. In the present double-blind study, the acute and chronic hemodynamic and clinical benefits of the calcium antagonist nisoldipine (= BAY K 5552) were compared with captopril in the adjunctive treatment of patients with heart failure (NYHA III or IV). The study group consisted of 17 patients. After randomization, 9 were treated with captopril (25 mg orally t.i.d.) and 8 with nisoldipine (3 were given 20 mg orally t.i.d., and 5 were given 20 mg b.i.d.). The following hemodynamic variables were obtained in the control phase after 3 days and 3 months' duration of treatment: heart rate, LVEF, SVI, ESVI, EDVI, PSP/ESVI (ratio of peak systolic pressure and end-systolic volume index), CI and systemic vascular resistance. The clinical status of the patients was assessed by means of seven criteria on an arbitrary scale. The following results were obtained: for the nisoldipine group, the average LVEF increased significantly from 0.26 to 0.31 within 3 days of treatment, but after 3 months, this increase had disappeared. All other hemodynamic parameters did not change significantly within either 3 days or 3 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Capillary density and oxygen supply in human dilated cardiomyopathy.

Human hearts with dilated cardiomyopathy (DCM) exhibit a hypertrophy of the myocytes; consequently, the intercapillary distance increases, which may impede the diffusionable metabolic supply. Therefore in the following study the microcirculation of living human hearts with DCM, excised during cardiac transplantation, was investigated. The hearts were reperfused with a FITC-stained salt-solution, this allowed the precise detection of all plasma perfused capillaries. Thus, functional capillary density, capillary distribution and its effect on oxygen supply could be determined. In eight human hearts, the average functional capillary density amounted to 1245 +/- 345 capillaries/mm2, while 50% of the tissue was within 12 micron from the nearest capillary. However, a small portion of the tissue (1%) might become anoxic under the assumption of a simple oxygen diffusion model. The results favor the view that capillary density is low in human DCM and tissue is at the border of hypoxia.

Biological Availability↗

[Verapamil, diltiazem or nifedipine in severe left ventricular functional disorder? A comparative study of the immediate hemodynamic effects].

High doses of verapamil, diltiazem or nifedipin were administered to three groups of eight patients each, with severely abnormal left-ventricular (LV) function (mean ejection fraction 0.29). Various haemodynamic measurements were made immediately before and 30 minutes after drug administration: LV ejection fraction, ratio of peak systolic pressure to endsystolic volume index, stroke index, pulmonary capillary closing pressure, and maximal diastolic filling rate. None of these were reduced. In fact, ejection fraction rose by a mean of 0.05, stroke index by a mean of 5 ml/m2, while p.c. closing pressure and contractility did not alter significantly. Verapamil and diltiazem reduced the pressure X rate product (an important determinant of oxygen consumption); nifedipine reduced total systemic resistance. It is concluded that verapamil and diltiazem can be used with advantage in cases of unstable angina, if there are severe abnormalities of LV function; they are to be preferred to beta-blockers in this situation. Nifedipin is the calcium antagonist of choice in hypertension and abnormal LV function.

Adult↗

A new technique for measuring oxygen saturations of hemoglobin and myoglobin and its application in open heart surgery.

Light reflected from the human heart surface was used to determine mixed hemoglobin and myoglobin oxygen saturations (O2SAT) in the cardiac tissue. The measurements were performed in 8 patients with coronary heart disease including stenosis of left anterior descending coronary artery (LAD) who underwent aorto-coronary bypass surgery. At the end of the operation the O2SAT was measured in the supply area of the LAD either with patent or occluded coronary bypass. In 13 experiments occlusion of the bypass resulted in a decrease of O2SAT from 74 +/- 16% to 61 +/- 24% (p less than 0.02). A new technique is introduced and its limitations are discussed. Preliminary results of application in coronary bypass surgery demonstrate an increase in tissue oxygenation following myocardial revascularization.

Coronary Artery Bypass↗

Spontaneous hemodynamic improvement or stabilization and associated biopsy findings in patients with congestive cardiomyopathy.

The hemodynamic courses of 56 patients with congestive cardiomyopathy (CCM) were investigated. Fourteen patients died within 24 months after diagnosis. The hemodynamic courses of the remaining 42 patients were investigated in subsequent examinations by determination of left ventricular ejection fraction (LVEF), mean pulmonary arterial pressure at maximal workload, and peak systolic pressure/end-systolic volume index. During the study interval of 32.2 +/- 20.0 months the conditions of 20 patients (48%) deteriorated, according to their hemodynamic status, and at least five of these died of terminal heart failure. Surprisingly, the conditions of 22 patients (52%) improved or stabilized. One of these died of leukemia. Seven patients in the latter group with initial LVEFs of 0.30 or less experienced an average increase from 0.22 to 0.51. Retrospectively consideration of age, alcohol intake, exercise capacity, and hemodynamic status were not helpful in predicting the course of the disease. In 38 patients endomyocardial biopsy samples could be obtained at the time of diagnosis. Reduced myofibril volume fraction (less than 60%) had prognostic significance for both hemodynamic deterioration and death (sensitivity 23/24 = 96%), while 14 of 15 patients whose conditions improved or stabilized had a myofibril volume fraction of 60% or more (specificity 14/15 or 93%, p less than .002). A relationship between hemodynamic status and the myofibril volume fraction could not be found. Individual patients with CCM differ significantly with respect to course of the disease. A distinct separation of the patients by means of morphologic criteria is possible. This makes it more likely that the pathogenesis of the disease is not unique.

Adolescent↗