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Biomedical subjects

C Holubarsch

Publications and source records attributed to C Holubarsch.

At least 73 records · Page 4Linked to original sources
PubMed1989

Influence of enoximone on myocardial energetics in patients with idiopathic dilated cardiomyopathy: comparison with nitroprusside.

Enoximone may influence myocardial energetics by vasodilation, which may reduce and by inotropism which may increase myocardial energy demand. To separate both pharmacological properties, the influence of enoximone on myocardial oxygen consumption and its hemodynamic determinants was analyzed and compared to the effects of the pure vasodilator nitroprusside. The relationship between myocardial oxygen consumption and left ventricular hemodynamics was evaluated in 22 patients with idiopathic dilated cardiomyopathy (NYHA stages II-III). During control, myocardial oxygen consumption per beat [MVO2 (beat)] correlated closely with left ventricular systolic stress-time integral (STI) (r = 0.74; p less than 0.001). The ratio of MVO2 (beat) and STI was used as an inverse measure of the economy of myocardial contraction. Following nitroprusside (10 patients) the STI decreased by 35% (p less than 0.005) and MVO2 (beat) by 30% (p less than 0.005). MVO2 (beat)/STI did not significantly change. Following enoximone (12 patients), STI decreased by 60% (p less than 0.001), MVO2 (beat) by 19% (p less than 0.001), and MVO2 (beat)/STI increased from 1.31 +/- 0.16 to 2.72 +/- 0.78 nl.cm2/100 g.dyn.s (p less than 0.001). In summary, vasodilation by nitroprusside decreased MVO2 (beat) in proportion to its major determinant, STI; the economy of myocardial contraction remained unchanged. Compared to nitroprusside, enoximone reduced the economy of contraction. Thus, with enoximone, the energy-saving effect of vasodilation is counteracted by increased energy demand due to the inotropic stimulation of the myocardium. Global myocardial oxygen consumption depends on the balance of both pharmacological properties.

Cardiomyopathy, Dilated↗
PubMed1988

Influence of enoximone and UDCG-115 on coronary hemodynamics in idiopathic dilated cardiomyopathy.

Coronary hemodynamics were studied in 24 patients with idiopathic dilated cardiomyopathy and in 17 patients without any significant heart disease under resting conditions using the argon method. Neither myocardial blood flow normalized for 100 g muscle tissue nor myocardial oxygen consumption per minute (MVO2) or oxygen supply-demand ratio were different between these 2 groups of patients. When enoximone (1 to 2 mg/kg body weight) was given intravenously in patients with idiopathic dilated cardiomyopathy, myocardial oxygen consumption decreased by only 8% (difference not significant), whereas a significant (p less than 0.05) 26% decrease of myocardial oxygen consumption was observed after UDCG-115 (1.25 mg/hour intravenously). However, with both substances the oxygen supply-demand ratio significantly increased from 1.46 +/- 0.10 to 1.57 +/- 0.20 (p less than 0.025; enoximone) and from 1.40 +/- 0.08 to 1.56 +/- 0.19 (p less than 0.05; UDCG-115), respectively. It is concluded from these data that (1) resting coronary hemodynamics related to a unit of myocardium are not different between normal and idiopathic dilated cardiomyopathy, and (2) phosphodiesterase inhibitors exert beneficial effects on coronary hemodynamics by improving the oxygen supply-demand ratio.

Cardiomyopathy, Dilated↗
PubMed1988

[Therapy of heart failure with vasodilator agents].

Vasodilation in congestive heart failure is an established therapeutic principal. The ventricular unloading improves contractile geometry and thereby improves working conditions for the contractile element: myocardial oxygen consumption falls and myocardial efficiency improves. This effect is independent from the vasodilating substance employed; it is, however, dependent on the simultaneous induction of pre- and afterload reduction. Vasodilation improves regional perfusion. Differential improvement in organ bloodflow is related to the type of vasodilator employed. It seems essential for a therapeutic benefit that renal and coronary perfusion are improved and that shunt flow, especially with steal phenomena, is avoided. Skeletal muscle bloodflow improves only slowly under ACE-inhibitor therapy. It could be shown that the immediate vasodilation due to ACE inhibition is followed by a second phase of vasodilation, which may be related to the influence of ACE inhibition of intraarterial wall angiotensin converting enzyme. Another factor possibly responsible for the delayed response to vasodilation in congestive heart failure, may be functional and structural changes in skeletal muscle. Reversal of these changes requires time. Both factors - the vessel wall related mechanism, as well as changes in parenchymal structure and function - require prolonged periods of treatment until therapeutic benefit can be seen.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Evaluation of long-term oral levodopa therapy in chronic congestive heart failure.

To evaluate the long-term effects of orally administered levodopa, 11 patients with chronic congestive heart failure (NYHA III-IV) were studied during maintenance therapy (30 +/- 1 days) and after withdrawal from levodopa. The daily levodopa dose was 4 g in six patients; because of side effects the levodopa dose was reduced to 2-3 g in the remaining patients. After withdrawal of levodopa, mean pulmonary capillary wedge pressure and mean right atrial pressure increased significantly (from 19 +/- 2 to 24 +/- 3 and from 7 +/- 2 to 9 +/- 2 mmHg, respectively). Effective renal plasma flow was 329 +/- 57 during levodopa therapy and decreased significantly to 252 +/- 27 ml/min after withdrawal of levodopa. The number of ventricular premature contractions and couplets increased during levodopa therapy and decreased again significantly after withdrawal of levodopa. No significant differences between on and off levodopa were observed in resting heart rate, arterial blood pressure, cardiac index, stroke work index, systemic vascular resistance, sodium and water excretion, or creatinine clearance. Seven patients improved on levodopa therapy by one NYHA class; four of these seven patients deteriorated again by one NYHA class after withdrawal of levodopa. Regarding both clinical and hemodynamic changes after withdrawal of levodopa, three patients were classified as responders to long-term levodopa therapy. All three responders received 4 g levodopa per day. Average dopamine plasma level was 5.3 +/- 0.8 ng/ml in the responder group and 2.0 +/- 0.5 ng/ml in the nonresponder group. Long-term administration of oral levodopa is associated with beneficial clinical and hemodynamic response in only a minority of patients with chronic congestive heart failure.

Administration, Oral↗
PubMed1987

Cardiac energetics after intravenous enoximone in idiopathic dilated cardiomyopathy.

The acute effects of enoximone on left ventricular (LV) function, myocardial oxygen metabolism and central and systemic hemodynamics were investigated in 12 patients with idiopathic dilated cardiomyopathy. Enoximone was administered intravenously at a rate of 12.5 mg/min; the average dose was 1.42 mg/kg. LV systolic pressure decreased significantly (p less than 0.01) from 128 +/- 18 to 96 +/- 16 mm Hg (mean +/- standard deviation), LV end-diastolic pressure from 16 +/- 3 to 5 +/- 3 mm Hg, LV end-diastolic volume from 288 +/- 43 to 210 +/- 58 ml, LV end-diastolic wall stress from 33 +/- 15 to 11 +/- 5 10(3) dynes/cm2 and LV peak systolic wall stress from 243 +/- 73 to 159 +/- 42 10(3) dynes/cm2. Heart rate increased from 86 +/- 18 to 100 +/- 20 beats/min, ejection fraction from 43 +/- 7 to 52 +/- 14% (p less than 0.05). Cardiac index, stroke volume index and dP/dtmax did not change significantly. Systemic vascular resistance decreased significantly (p less than 0.01) from 1,311 +/- 444 to 1,027 +/- 356 dynes s cm-5, mean pulmonary artery pressure from 13 +/- 6 to 8 +/- 2 mm Hg, mean right atrial pressure from 4 +/- 2 to 2.6 +/- 2 mm Hg and mean arterial pressure from 95 +/- 13 to 74 +/- 13 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide.

The influence of cardiac function on the diuretic and hemodynamic effects of the loop diuretic piretanide was investigated in nine patients with congestive heart failure. The diuretic response to piretanide correlated significantly with the pretreatment cardiac index (r = 0.90). Furthermore, a significant correlation was found between the pretreatment fractional sodium excretion and the cardiac index (r = 0.85). The fractional sodium excretion is reciprocal to the renal sodium and water reabsorption. No change in the hemodynamics was observed prior to the onset of diuresis. At 120 minutes after administration of piretanide, the reduction of mean pulmonary capillary wedge pressure (r = 0.88) and mean right atrial pressure (r = 0.80) was significantly related to the diuretic response. We conclude that the reduced diuretic response to piretanide in patients with low cardiac index is due to increased renal sodium and water reabsorption. The hemodynamic changes following the administration of piretanide are dependent on the diuresis.

Adult↗
PubMed1987

Hemodynamics and myocardial oxygen metabolism of pulsus alternans in patients with dilative cardiomyopathy.

The hemodynamic and myocardial energetic changes due to pulsus alternans were investigated by left and right heart catheterization and by oxygen consumption measurements in three patients with dilative cardiomyopathy. In all three patients, pulsus alternans developed after intravenous administration of the phosphodiesterase inhibitor enoximone. Following enoximone (Patients 1/2/3), left ventricular peak systolic pressure was reduced, in the respective patients, from 100/103/115 mmHg (normal beat) to 91/96/94 mmHg (strong beat) and further to 59/80/85 mmHg (weak beat); left ventricular end-diastolic pressure was reduced from 24/23/22 mmHg (normal beat) to 5/10/6 mmHg (strong beat) and further to 3/7/4 mmHg (weak beat). Cardiac output increased by an average of 16%. Heart rate increased by an average of 12%. Stroke work (during pulsus alternans mean between strong and weak beats) did not change (less than 5%) in any of the three patients. Arterial-coronary-sinus oxygen content difference decreased by 5%/13%/22, respectively. Myocardial oxygen consumption per beat decreased in Patient 1 by 8%, in Patient 2 by 8% and remained unchanged in Patient 3. It is concluded that pulsus alternans occurred in consequence of alternating systolic performance. The alternation in systolic performance most probably resulted from a disturbance in excitation-contraction coupling induced by enoximone. The pronounced reduction of left ventricular preload following administration of enoximone may have augmented further the differences between the strong and the weak beat. A disturbance in myocardial oxygen metabolism was ruled out as the cause of pulsus alternans in these patients.

Adult↗
PubMed1987

Energetic aspects of inotropic interventions in rat myocardium.

Contractile force of the myocardium can be increased by different molecular mechanisms, and therefore different energetic consequences may result. The influence of the inotropic substances isoproterenol and UDCG-115 on myocardial energetics in isometrically contracting left ventricular rat papillary muscles was investigated by means of highly sensitive antimony bismuth thermopiles. Isoproterenol increased total heat and initial heat by 147% (p less than 0.01) and 69% (p less than 0.02) when normalized to tension-time integral, respectively. No significant change of both heat terms occurred due to UDCG-115. Initial heat was separated into tension-independent heat ("calcium cycling") and tension-dependent heat ("cross-bridge cycling") by means of a new method using 2,3-butanedione monoxime. Both tension-dependent heat per tension-time integral and tension-independent heat increased significantly, due to isoproterenol, from 4.9 +/- 1.17 to 7.6 +/- 2.72 mu cal/g.cm.s (p less than 0.05) and from 0.15 +/- 0.06 to 0.22 +/- 0.04 mcal/g (p less than 0.01). UDCG-115 influenced neither tension-independent heat nor tension-dependent heat per tension-time integral significantly. Thus, the economy of force development was not significantly altered due to UDCG-115 whereas isoproterenol significantly increased the energy necessary for activation, i.e. calcium cycling, and the energy necessary for force production, i.e. cross-bridge cycling. The basic mechanisms of these energetic changes are discussed.

Animals↗
PubMed1987

Changes in myocardial distensibility in rat papillary muscle: fibrosis, KCl contracture, hypoxic contracture, oxygen and glucose deficiency contracture, and experimental tetanus.

We describe diastolic properties of the myocardium in terms of stress-strain relations. In a mathematical analysis, the equation sigma = alpha(e beta.epsilon-1) of the stress-strain curve can be changed by an increase in the exponent beta or the multiplicative constant alpha. It can be experimentally shown that in hypertrophied myocardium of rats with essential hypertension and renal hypertension (SHR and Goldblatt rats, respectively), the steepening of the stress-strain curve is associated with an increase in the exponent beta (stiffness constant) and an enhancement of collagen content. On the other hand, in acute hypoxic myocardium, the slope of the stress-strain curve is increased without a significant change of the exponent beta. Our results from heat measurements and quick-release experiments indicate that the hypoxic contracture (H) and the oxygen and glucose deficiency contracture (HG) are in contrast to the results of depolarization contracture (KCl) and experimental tetanus (T). In H and HG, the cross-bridge cycling rate was found to be slowed by a factor of 2,000 compared to KCl and T. This means that ATP demand for force development and maintenance is 2,000 times less in H and HG than in KCl and T. We will further discuss the meaning and implications of these experimental findings.

Animals↗
PubMed1987

Acute and chronic changes of myocardial energetics in the mammalian and human heart.

In earlier studies using papillary muscles of the rat left ventricle and highly sensitive thermopiles we demonstrated that the heat liberated per gram of myocardium per unit of developed tension-time integral is decreased when the rats suffered from hypothyroidism or renal hypertension. This increase in economy of force production was shown to be associated with a decrease in myosin-ATPase activity and a change in isomyosin composition. In a recent study we showed an increase in heat per gram of mammalian myocardium per tension-time integral of 70% after application of isoproterenol. In order to study the relationship between energy costs and developed tension-time integral in the human heart, haemodynamics and myocardial oxygen consumption were measured. The data were obtained using a Millar microtip catheter pressure transducer and the argon method. Haemodynamics and myocardial energetics were analysed in 8 patients without significant heart disease before and after application of isoproterenol and in 10 patients with dilative cardiomyopathy (NYHA II-III). During one cardiac cycle, myocardial oxygen consumption per gram of LV myocardium per beat (MVO2/g x beat) is related to LV stress-time integral (integral of sigma xt). The economy of myocardial contraction (EC) was calculated by (formula; see text) EC was 11.3 +/- 3.2 in normal and 14.3 +/- 4.7 dyn x s x g/cm2 x mu cal in dilative cardiomyopathic hearts (NS). Isoproterenol decreased EC from 11.3 +/- 3.2 to 5.5 +/- 1.6 dyn x s x g/cm2 x mu cal in the normal hearts (p less than 0.01). In the rat myocardium, changes in economy of force generation were found due to catecholamines, pressure overload and hypothyroidism. In the human heart, similar energetic changes were observed due to catecholamines. No significant differences in energy of force production were seen between normal and dilative cardiomyopathic hearts. The effect of catecholamines in the mammalian and human myocardium is explained by changes in activation processes and in chemomechanical energy transduction at the level of the contractile proteins.

Acute Disease↗
PubMed1987

Influence of phosphodiesterase inhibition on myocardial energetics in dilative cardiomyopathy.

The effects of inhibition of phosphodiesterase by enoximone on left ventricular haemodynamics and myocardial energetics were investigated in 10 patients with idiopathic dilative cardiomyopathy. After intravenous administration of enoximone, there was a significant reduction of left ventricular systolic pressure from 126 +/- 21 to 93 +/- 16 mm Hg, of left ventricular end-diastolic pressure from 16 +/- 8 to 5 +/- 3 mm Hg and of left ventricular end-diastolic volume from 287 +/- 54 to 215 +/- 69 ml. Left ventricular pressure-volume work decreased significantly from 12.1 +/- 3.6 to 7.6 +/- 2.8 mm Hg.l. Heart rate was 87 +/- 17 before and 103 +/- 18 min-1 after administration of enoximone (p less than 0.01). Left ventricular systolic stress-time integral, a major determinant of myocardial oxygen consumption, decreased by 49% from 91 +/- 32 to 46 +/- 15 10(3) dyn.s/cm2 (p less than 0.01). In contrast myocardial oxygen consumption per beat was reduced by only 18%, from 138 +/- 28 to 113 +/- 17 microliters O2/100 g (p less than 0.01). The economy of myocardial contraction as calculated by the ratio of systolic stress-time integral to myocardial oxygen consumption per beat was 675 +/- 192 before and 370 +/- 128 dyn.s.100 g/cm2.microliter O2 after administration of enoximone. In conclusion, the phosphodiesterase inhibitor enoximone exhibits vascular and myocardial effects. The myocardial effects result in decreased economy of myocardial contraction. The possible molecular mechanisms of these energetic changes are discussed.

Cardiomyopathies↗
PubMed1987

Estimation of left ventricular volume and mass by magnetic resonance imaging: comparison with quantitative biplane angiocardiography.

Magnetic resonance imaging (MRI) is well suited for the delineation of cardiac anatomy. In this study an estimation of left ventricular volume and muscle mass by MRI was attempted, using an iron-shielded resistance magnet (Bruker) with 0.23 T. Images were obtained with ECG gating. For image-processing our own software program was used. Slice images were 8 mm thick and spaced 16 mm. Volumes were standardized for a "normal" LV. Muscle mass was calculated directly from the systolic image as the difference between inner and outer ventricular outline. There was a wide range of volumes and mass (100-300 ml, 200-500 g). For comparison and validation conventional biplane left ventriculography was used. Fourteen patients were studied with MRI, but satisfactory studies were obtained in only 7. Correlation of MRI and angiographic volumes was good (r = 0.84). For left ventricular mass it was excellent (r = 0.94). Ventricular walls and cavities were clearly outlined. Even minor details of anatomy were recognized. Limitations of MR study included a narrow space for the patient within the system and the long duration of data acquisition time.

Adult↗
PubMed1987

Tolerance to hypoxia of myocardium from adult and aged spontaneously hypertensive rats.

Myocardial mechanics and high-energy phosphate content [ATP and creatine phosphate (CrP)] of isolated left ventricular papillary muscle preparations from male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were compared at 6 and 18 mo of age. In comparison with oxygenated (95% O2-5% CO2) glucose-supplied (5.5 mM) papillary muscles from hearts of WKY rats, papillary muscles from hypertrophied hearts of the 18-mo-old SHR exhibited a prolonged time to peak tension, electromechanical delay time, and an increase in resting tension measured at the apex of the length-tension curve. Adenine nucleotide (ATP and ADP) contents of oxygenated papillary muscles were not significantly different between SHR and WKY strains at 6 or 18 mo of age, but CrP content of hearts from adult WKY and SHR were higher than for aged WKY and SHR rats. For up to 30 min of hypoxia (95% N2-5% CO2), muscles from the 18-mo-old SHR and WKY rats demonstrated improved tolerance to hypoxia compared with muscles from younger animals. However, at 60 min of hypoxia the 18-mo-old SHR demonstrated lower active tension and adenylate energy charge [(1/2 ADP + ATP)/(ATP + ADP + AMP)]. At higher glucose concentrations (22 mM), both 18-mo-old WKY and SHR demonstrated improved tolerance to hypoxia; moreover, the differences between strains were no longer evident. Following reoxygenation with 5.5 mM glucose, contracture tension and CrP content recovered to near prehypoxic control levels, whereas developed tension and ATP content remained moderately depressed for all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

[Acute effects of nitroglycerin on the energetics of the human left ventricular myocardium].

We analyzed performance and efficiency of the left ventricular myocardium on the basis of two new energetic parameters. The myocardial energy consumed during one cardiac cycle is related to performed work on the one hand (E1) and to the stress-time-integral on the other (E2). E1 was obtained by analysis of the pressure-volume integral divided by left ventricular muscle mass. E2 was obtained as follows: the stress-time integral was analyzed from pressure-volume data and wall thickness using an ellipsoidal calculation model. In order to transfer the stress-time integral into energy units, the value was multiplied by a constant factor which was obtained in experimental myothermal studies. In ten patients with coronary heart disease undergoing diagnostic heart catheterization, angiocardiography was performed before and after oral administration of nitroglycerin (1.6 mg). Total energy consumption (2E1 + E2) per gram myocardium per beat decreased from 6.1 +/- 1.3 mcal/g to 4.7 +/- 1.4 mcal/g (P less than 0.01), and myocardial efficiency (E1/[2E1 + E2]) increased from 27.0 +/- 3.1% to 28.4 +/- 4.3% (N.S.) on the average. This analysis explains quantitatively the beneficial effect of nitro-preparations on myocardial function and energetics.

Adult↗
PubMed1986

Assessment of myocardial function by calculation of two energetic parameters from pressure-volume relations and wall thickness in human ventricles.

For defining myocardial performance in chronic cardiac diseases and during acute pharmacological interventions we created a new index of performance based on myocardial mechanical and energetic counterparts. From angiocardiographic pressure-volume data the pressure-volume integral is analyzed and divided by left ventricular muscle mass, yielding work done by a unit of myocardium (E1). From pressure-volume data the stress-time integral integral of sigma.t is evaluated by using an ellipsoidal calculation model. In order to compare E1 with the integral of sigma.t the integral of sigma.t is transformed into energetic units on the basis of new physiologic myothermal findings (E2). Then, the sum of E1 and E2 (i.e.,the maximum of mechanical performance), the ratio of E1 to the sum of E1 and E2 can be defined (i.e., the myocardial work related to the energy consumed during a contraction). By calculating E1 and E2, we are able to analyze the myocardial efficiency of work production. These parameters are proposed for judging the myocardial performance and efficiency in congestive heart failure and the effects of positive inotropic substances and vasodilators.

Angiocardiography↗