Biomedical subjects

C Holubarsch

Publications and source records attributed to C Holubarsch.

At least 55 records · Page 3Linked to original sources

PubMed1992

[Biochemical changes and disorders of electromechanical coupling in chronic heart failure].

In the chronically failing heart, subtle biochemical alterations occur at the level of a number of subcellular systems. The cellular elements that control activation and inactivation of the contractile proteins are the plasma membrane and the sarcoplasmic reticulum (SR). During the plateau phase of the action potential the slow calcium channel is activated so that calcium ions enter into the interior of the cell and initiate--as a trigger signal in loco--the calcium release from the SR-calcium-stores. In the absence of catecholamines the measured calcium ion currents are similar when normal human myocardium is compared to end-stage failing human myocardium. However, the increase in the calcium ion currents induced by maximum concentrations of catecholamines is significantly smaller in failing myocardium compared to normal myocardium. This observation can easily be explained by the down-regulation of the beta-1-adrenoceptors and the increase in the inhibitory Gi-proteins. In the failing myocardium, therefore, a beta-1-adrenoceptor stimulation leads to an insufficient increase in cyclic adenosine monophosphate so that the opening probability of the calcium channels is not appropriately enhanced. This results in a decreased contractile reserve. As far as is known today, the inactivation mechanisms of the plasma membrane (sodium-calcium-exchanger, sodium-potassium ATPase, calcium ATPase) are not disturbed in the failing human myocardium. The calcium release from the SR can be quantified using either calcium indicators (aequorin, fura 2) or highly sensitive thermopiles. Both sophisticated heat measurements and fura-2 measurements indicated a decreased systolic calcium ion concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The heart in heart failure. Ventricular and myocardial alterations.

In heart failure, many alterations occur in the ventricle as a whole, as well as in the myocardial cell. In the first part of this review we report on the macroscopic structure of the left ventricle by analysing the relation between left ventricular dilatation and left ventricular hypertrophy in terms of ventricular wall stress. Peak systolic stress in dilated ventricles of patients with compensated heart failure does not differ from values obtained in normal ventricles, whereas the systolic stress-time integral is increased by more than 40%. The stress-time integral is a major determinant of myocardial oxygen consumption, and its reduction by peripheral vasodilation leads to a proportional decrease in left ventricular oxygen consumption. In contrast, the phosphodiesterase inhibitor, enoximone, decreases the stress-time integral without a proportional decrease in myocardial oxygen consumption, due to the competition between positive inotropic effect with increased oxygen consumption and a vasodilating effect with decreased oxygen consumption. Beta-1 adrenoceptor agonists increase myocardial oxygen consumption. In the second part of this review we report on the functional alterations of the following subcellular and molecular structures in the failing myocardium: (1) adrenoceptors and G-proteins; (2) sarcoplasmic reticulum with an altered force-frequency relationship; (3) the acto-myosin system with decreased velocity of shortening and increased economy of force generation. On the basis of these alterations, a disadvantageous chain of events develops in the failing myocardial cell.

Cardiomegaly↗

PubMed1991

The effect of the partial beta-1-adrenoceptor agonist xamoterol on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy.

Xamoterol, a new partial beta 1-adrenoceptor agonist, was evaluated in respect to its hemodynamic and energetic effects when given acutely i.v. (0.2 mg/kg body weight) to 10 patients with idiopathic dilated cardiomyopathy. Hemodynamically, a small drop in left ventricular end-systolic volume index (from 105 +/- 38 to 91 +/- 48 ml/m2; p less than 0.05) and end-diastolic volume index (from 168 +/- 44 to 152 +/- 41 ml/m2; p less than 0.05) and an increase in maximum rate of left ventricular pressure rise (from 1,003 +/- 358 to 1,283 +/- 398 mm Hg/s; p less than 0.001) was observed. The systolic stress-time integral was only slightly reduced after injection of xamoterol, from 107 +/- 28 to 94 +/- 35 x 10(3) dyn.s/cm2 (NS). Other conventional hemodynamic variables did not change significantly. Myocardial oxygen consumption per beat increased from 125 +/- 39 microliters/beat/100 g to 153 +/- 62 microliters/beat/100 g (p less than 0.05). The ratio of myocardial oxygen consumption per beat and stress-time integral--as an inverse measure of left ventricular contraction economy--increased significantly, from 132 +/- 62 to 192 +/- 115 microliters/beat/10(3) dyn.s/cm2 (p less than 0.02) after injection of xamoterol, whereas left ventricular efficiency decreased from 17.6 +/- 7.8 to 13.8 +/- 6.5% (p less than 0.05). Thus, in idiopathic dilated cardiomyopathy, xamoterol exhibited only minor hemodynamic effects whereas myocardial contraction economy and efficiency were significantly reduced.

Adult↗

PubMed1991

Energetics of isometric force development in control and volume-overload human myocardium. Comparison with animal species.

Alteration in crossbridge behavior and myocardial performance have been associated with myosin isoenzyme composition in animal models of myocardial hypertrophy or atrophy. In the hypertrophied human heart, myocardial performance is altered without significant changes in myosin isoenzymes. To better understand this discrepancy, isometric heat and force measurements were carried out in 1) control and volume-overload human myocardium, 2) control, pressure-overload, and hyperthyroid rabbit myocardium, and 3) control and hypothyroid rat myocardium. In control human myocardium, peak isometric twitch tension was 44.0 +/- 11.7 mN/mm2, and maximum rate of tension rise was 69.2 +/- 21.0 mN/sec.mm2. In volume-overload human myocardium, peak twitch tension and maximum rate of tension rise were reduced by 55% (p less than 0.05) and 65% (p less than 0.05), respectively. The average force-time integral of the individual crossbridge cycle, calculated by myothermal techniques, was increased by 85% (p less than 0.005) in volume-overload human myocardium. In control and hormonally altered myocardium, both across and within species (control human, control rat, control rabbit, hypothyroid rat, and hyperthyroid rabbit), there was a close relation between the crossbridge force-time integral and the percentage of V3-type myosin isoenzyme in the myocardium. However, hemodynamically altered (volume-overload human and pressure-overload rabbit) myocardium did not follow this relation. Across and within species, there were significant correlations between maximum rate of tension rise and average tension-dependent heat rate (r = 0.97, p less than 0.001) and between maximum rate of tension fall and average tension-independent heat rate (r = 0.82; p less than 0.025). Furthermore, there were close inverse relations between these heat rates and the crossbridge force-time integral. In addition, there was an inverse relation between tension-independent heat and the crossbridge force-time integral. Across and within species total myocardial energy turnover was significantly correlated with the crossbridge force-time integral (relative total heat, r = -0.84, p less than 0.02; relative total-activity related heat, r = -0.88, p less than 0.01). The present findings indicate that 1) factors separate from myosin isoenzymes account for the altered crossbridge cycle in volume-overload human and pressure-overload rabbit myocardium, 2) changes in excitation-contraction coupling processes accompany changes in the crossbridge cycle within and across species, and 3) the force-time integral of the crossbridge cycle is a major determinant of total myocardial energy turnover.

Animals↗

PubMed1991

Left ventricular geometry, myocardial function and energetics of the dilated left ventricle. Influence of vasodilators and positive inotropic substances.

Vasodilators have been shown to improve hemodynamics of the failing heart as a short-term effect and to decrease mortality as a long-term result. We therefore studied the effect of different vasodilators on myocardial mechanics and energetics in patients with idiopathic dilated cardiomyopathy (IDC) NYHA II to III. In these patients undergoing routine heart catheterization myocardial oxygen consumption was measured using the argon method, and left ventricular pressure and geometry were obtained from left ventricular angiography using a Millar tip microcatheter. All data were analyzed for one single heart beat. The best correlation was found between MVO2/beat and the systolic stress-time integral which considers left ventricular pressure, wall thickness, and geometry. The relation between MVO2/beat and peak systolic wall stress was less relevant. No correlation was found between MVO2/beat and pressure-volume work, dP/dtmax, and mean velocity of circumferential fiber shortening. The intravenous application of nitroprusside and the ACE-inhibitor benazepril decreased both the systolic stress-time integral and the myocardial oxygen consumption in proportion to each other indicating unchanged economy of myocardial contraction. In contrast to other vasodilators, beta 1-agonists and phosphodiesterase inhibitors increase myocardial oxygen consumption independently of changes in the stress-time integral. In conclusion, vasodilators decrease left ventricular pressure and chamber size and thereby proportionally reduce MVO2/beat. The reduction of energy needed for myocardial contraction may partially explain the long-term effects of the ACE-inhibitors and combinations of vasodilators. Pure positive inotropic substances, especially beta 1-agonists, increase myocardial oxygen consumption with minor changes of systolic stress-time integral.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Volume↗

PubMed1991

Energetic consequences of substances currently used or recommended for long-term treatment of chronic heart failure.

Vasodilators have been shown to improve hemodynamics of the failing heart as a short-term effect, and to decrease mortality as a long-term result. We, therefore, studied the effects of vasodilators and inotropic agents on myocardial mechanics and energetics in patients with congestive heart failure New York Heart Association (NYHA) classes II-III. In these patients, who underwent routine heart catheterization, myocardial oxygen consumption was measured using the argon method, and LV pressure and geometry were obtained from LV angiography using a Millar microtipped catheter. All data were analyzed for one single heart beat. The best correlation was found between MVO2/beat and the systolic stress-time integral which considers LV pressure, LV wall thickness, and LV geometry. The relation between MVO2/beat and peak systolic wall stress was less relevant. No correlation was found between MVO2/beat and pressure-volume work, dP/dtmax, and mean velocity of circumferential fiber shortening. The intravenous application of nitroprusside and the ACE-inhibitor benazepril decreased both the systolic stress-time integral and the myocardial oxygen consumption in proportion to each other, indicating unchanged economy of myocardial contraction. In contrast, beta 1-agonists and phosphodiesterase inhibitors increased myocardial oxygen consumption independently of changes in the stress-time integral. In conclusion, vasodilators decrease LV pressure and chamber size and thereby proportionally reduce MVO2/beat. The reduction of energy needed for myocardial contraction may partially explain the long-term effects of the ACE-inhibitors and combinations of vasodilators. Pure inotropic substances, especially beta 1-agonists, increase myocardial oxygen consumption with only minor changes of systolic stress-time integral.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzazepines↗

PubMed1991

[Vasodilatation and positive inotropic effect of the phosphodiesterase inhibitor enoximone].

The comparison of two invasive studies using intravenous application of the phosphodiesterase enoximone demonstrated unchanged cardiac output in patients with dilated cardiomyopathy NYHA II-III, and increased cardiac output (from 3.22 +/- 1.15 to 5.04 +/- 2.05 l/min; p less than 0.01) in acute heart failure. This comparison of hemodynamic parameters in addition to studies on myocardial oxygen consumption support the use of intravenous enoximone in acute heart failure, whereas the long-term application of enoximone in chronic heart failure is judged to be critical.

Cardiac Output↗

PubMed1990

Repeat determination of left ventricular wall thickness from mass and volume during one cardiac cycle for the calculation of left ventricular wall stress parameters.

Left ventricular end-diastolic wall stress, end-systolic wall stress, and systolic stress-time integral are important parameters to characterize left ventricular load and function. To obtain these parameters, left ventricular pressure, volume, and wall thickness data must be determined at short time intervals throughout one cardiac cycle. However, the measurement of wall thickness at short intervals (i.e., 20 ms) throughout a cardiac cycle is tedious. Furthermore, measurements of wall thickness are less accurate at end-systole compared with end-diastole. For these reasons we developed a computer program for calculating wall thickness at short intervals (20 ms) throughout the cardiac cycle from one single determination of left ventricular wall mass and repetitive measurements of left ventricular (LV) volume.

Computer Simulation↗

PubMed1990

The safety profile of ibopamine, an alternative substance for treatment of chronic heart failure.

Before a new drug can be recommended for treatment of chronic heart failure, efficacy and safety have to be fulfilled. In this paper, the safety aspect of ibopamine, a congener of dopamine, is investigated by reviewing the available reports on this drug. A trend towards reduced mortality was found for patients with chronic heart failure during long-term treatment. No change in the potassium serum concentration has been found, whereas the plasma renin activity, plasma norepinephrine levels and the aldosterone secretion were decreased. It is concluded that ibopamine is a safe drug which may become an interesting alternative or additive therapy for patients with chronic heart failure.

Cardiotonic Agents↗

PubMed1990

Catecholamine metabolism in patients with congestive heart failure under acute and chronic oral levodopa therapy.

Catecholamine metabolism was assessed in 14 patients with chronic congestive heart failure (NYHA class IV; cardiac index 2.4 +/- 0.2 l min-1, ejection fraction 20 +/- 11%) on levodopa (L-Dopa-ratiopharm) treatment: 1. prior to the start of levodopa treatment; 2. following acute administration of levodopa in the 14 patients and in 4 healthy control subjects; 3. after 30 days +/- 1 day with 2-4 g levodopa p.o. daily in the group of patients. Only a minority of the patients showed sustained clinical and/or hemodynamic improvement. Free and conjugated plasma dopamine and urinary/excretion of dopamine increased 20- to 40-fold in the group of patients and in the healthy control subjects subsequent to levodopa administration. An increase in noradrenaline and adrenaline levels (conjugated plasma fractions and urinary excretion of free noradrenaline and adrenaline) was only observed in the healthy control subjects, but not in the group of patients. Free noradrenaline and adrenaline plasma fractions did not show any significant change on levodopa treatment, either in the group of patients or in healthy control subjects. Clinical and hemodynamic changes seen on levodopa treatment are related to elevated dopamine concentrations. The lack of increase in noradrenaline and adrenaline in the group of patients may be related to reduced activity of dopamine-beta-hydroxylase in patients with congestive heart failure NYHA class IV.

Administration, Oral↗

PubMed1989

Influence of isoproterenol on myocardial energetics. Experimental and clinical investigations.

The influence of isoproterenol on myocardial performance and energetics was investigated in normal guinea pig myocardium and in patients with normal left ventricular function. The in vitro experiments were performed by simultaneous isometric force and heat measurements using sensitive antimony-bismuth thermopiles. Following the application of isoproterenol (10(-8) M) isometric peak twitch tension and tension-time integral increased significantly by 185% and 142%, respectively. Tension-independent heat which reflects high energy phosphate hydrolysis of excitation-contraction coupling increased by 183%. Tension-dependent heat reflecting the high energy phosphate hydrolysis of the crossbridges increased by 417%. The ratio of tension-dependent heat to tension-time integral increased by 131%. The recovery/initial heat ratio, reflecting the efficiency of the recovery metabolism, and the resting metabolism did not significantly change. In the patients the effect of isoproterenol on myocardial energetics was evaluated in terms of myocardial efficiency. Following isoproterenol administration, left ventricular systolic stress-time integral decreased by 49% due to reductions in end-diastolic pressure, end-diastolic volume and duration of systole. Pressure-volume work remained unchanged. Myocardial oxygen consumption per minute increased in proportion to heart rate. The ratio of myocardial oxygen consumption per beat to left ventricular systolic stress-time integral increased significantly by 95%. External myocardial efficiency was unaltered. Thus, isoproterenol increases the energy turnover of excitation-contraction coupling and increases the energy consumption of the crossbridges disproportionately to developed tension-time integral in the guinea pig heart.

Adult↗

PubMed1989

Influence of the calcium-sensitizer UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy. Comparison with nitroprusside.

UDCG-115 is a new cardiotonic agent which in vitro increases the sensitivity of the contractile proteins to calcium ions, inhibits the activity of phosphodiesterase, and prolongs the duration of the action potential. The influence of UDCG-115 (i.v.) on hemodynamics and myocardial energetics was investigated in patients with idiopathic dilated cardiomyopathy (NYHA II-III) and compared to the effects of the pure vasodilator nitroprusside. UDCG-115 increased cardiac index from 3.2 +/- 0.4 to 4.2 +/- 0.8 l/min/m2 (p less than 0.01) and decreased left ventricular end-diastolic wall stress (preload) from 52 +/- 21 to 28 +/- 18 10(3) dyn/cm2 (p less than 0.01) and end-systolic wall stress (afterload) from 201 +/- 61 to 129 +/- 43 10(3) dyn/cm2 (p less than 0.01) compared to control conditions. Compared to nitroprusside, for a similar decrease in preload and afterload. UDCG-115 increased cardiac index by 40% (p less than 0.01), stroke volume index by 37% (p less than 0.01) and maximum rate of left ventricular pressure rise by 23% (p less than 0.05). Heart rate did not significantly change with either drug. Myocardial oxygen consumption per beat decreased by 33% (p less than 0.05) with UDCG-115 and by 30% (p less than 0.01) with nitroprusside. With both drugs, the decrease of myocardial oxygen consumption correlated significantly with the decrease of left ventricular systolic stress-time integral. The slopes of the respective linear regression lines were not significantly different. Thus, UDCG-115 given intravenously in patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure exhibits significant inotropic and vasodilating properties. The systemic hemodynamic actions are associated with favorable effects on myocardial energetics.

Adult↗

PubMed1989

Separation between vasodilation and positive inotropism by assessment of myocardial energetics in patients with dilated cardiomyopathy.

Phosphodiesterase inhibitors have vasodilating and positive inotropic properties, and these compounds may have energy saving effects due to vasodilation and energy consuming effects due to inotropism. In order to differentiate between the effects, it is necessary to relate myocardial oxygen consumption to its hemodynamic determinants. Myocardial oxygen consumption per beat was related to the following parameters: dp/dtmax, mean velocity of fiber shortening, pressure-volume work, peak developed wall stress, and stress-time integral. The best linear relationship was found between myocardial oxygen consumption per beat and the corresponding stress-time integral (r = 0.71; p less than 0.001) in patients with idiopathic dilative cardiomyopathy. Using i.v. nitroprusside as a pure vasodilator, myocardial oxygen consumption per beat and stress-time integral decreased along this established relationship. In contrast, the phosphodiesterase inhibitor enoximone given intravenously decreased the stress-time integral significantly more than the myocardial oxygen consumption per beat. We conclude from these data that phosphodiesterase inhibitors possess vasodilating properties which reduce the myocardial oxygen demand. In addition, they do have positive inotropic effects which increase the myocardial oxygen demand. Myocardial oxygen consumption always reflects the sum of both effects. The balance between the energy saving and the energy consuming effects may determine the efficacy of phosphodiesterase inhibitors, especially in the long-term treatment of chronic heart failure.

Cardiomyopathy, Dilated↗

PubMed1989

Influence of UDCG-115 on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy.

The influence of the new inotropic and vasodilating agent UDCG-115 on hemodynamics and myocardial oxygen metabolism was investigated in 11 patients with idiopathic dilated cardiomyopathy (New York Heart Association class II to III). After intravenous administration of UDCG-115, cardiac index increased from 3.03 +/- 0.68 to 3.76 +/- 1.07 L/min/m2 (p less than 0.01), left ventricular ejection fraction increased from 31 +/- 13 to 39 +/- 16% (p less than 0.01), and maximum rate of left ventricular pressure rise increased from 935 +/- 248 to 1056 +/- 284 mm Hg/sec (p less than 0.05). Left ventricular end-diastolic wall stress (index of preload) and left ventricular end-systolic wall stress (index of afterload) decreased by 41% (p less than 0.01) and 34% (p less than 0.001), respectively. Heart rate did not change significantly. With UDCG-115 myocardial oxygen consumption decreased from 14.3 +/- 5.1 to 10.6 +/- 3.8 ml/min/100 gm (p less than 0.05), and the ratio of myocardial oxygen supply to myocardial oxygen demand increased from 1.40 +/- 0.08 to 1.53 +/- 0.17 (p less than 0.05). Thus intravenous UDCG-115 improves left ventricular function by increasing inotropism and reducing preload and afterload in patients with idiopathic dilated cardiomyopathy and moderate congestive heart failure. The systemic hemodynamic actions are associated with favorable effects on myocardial energetics.

Cardiomyopathy, Dilated↗

PubMed1989

Myocardial energetics in patients with dilated cardiomyopathy. Influence of nitroprusside and enoximone.

Cardiotonic agents influence myocardial energy consumption by vasodilation, which may reduce energy demand, and by inotropism, which may increase it. To distinguish between the two effects, myocardial oxygen consumption must be analyzed in relation to its hemodynamic determinants. The coupling of myocardial oxygen consumption with its determinants was investigated in 22 patients with idiopathic dilated cardiomyopathy (NYHA Class II and III). Predicted myocardial oxygen consumption by the pressure-work index, the Bretschneider index, and the pressure-volume area correlated moderately with measured myocardial oxygen consumption (r = 0.57, p less than 0.001; r = 0.52, p less than 0.005; and r = 0.63, p less than 0.001). Multiple regression analysis, including left ventricular peak systolic wall stress, systolic stress-time integral, pressure-volume work, maximum rate of left ventricular pressure rise, and mean velocity of circumferential fiber shortening indicated that systolic stress-time integral is the major determinant of myocardial oxygen consumption (r = 0.75, p less than 0.001) in these patients. Enoximone, a phosphodiesterase inhibitor, has an inotropic and a vasodilating effect. To investigate the inotropic portion of the energy cost of this phosphodiesterase inhibitor, the influence of enoximone on myocardial oxygen consumption and systolic stress-time integral was compared with the effects of nitroprusside, which is a vasodilator only. Nitroprusside (10 patients) and enoximone (12 patients) reduced left ventricular systolic stress-time integral from 109 +/- 22 to 71 +/- 21 (p less than 0.005) and from 104 +/- 23 to 42 +/- 10 (p less than 0.001) 10(3) dynes.sec/cm2, respectively. Myocardial oxygen consumption decreased from 159 +/- 44 to 112 +/- 23 (p less than 0.005) and from 134 +/- 28 to 109 +/- 21 (p less than 0.001) microliters/beat/100 g, respectively. In both groups, there was a significant correlation between the decrease in myocardial oxygen consumption and the decrease in systolic stress-time integral. The slopes of the respective linear regression lines were significantly different (1.27 for nitroprusside and 0.51 nl.cm2/100 g.dynes.sec for enoximone, p less than 0.05), indicating a smaller decrease of myocardial oxygen consumption for a given decrease of stress-time integral with enoximone. Applying the pressure-work index or the pressure-volume area instead of systolic stress-time integral yielded comparable results. Thus, vasodilation reduces myocardial oxygen consumption in proportion to the reduction of stress-time integral. With enoximone, the energy-saving effect of vasodilation is counteracted in part by the increased energy d

Adult↗

PubMed1989

Influence of the positive inotropic substance pimobendan (UD-CG 115 BS) on contractile economy of guinea pig papillary muscles.

Using antimony-bismuth myothermal equipment, we measured simultaneously the initial heat liberated from and the stress-time integral developed by guinea pig papillary muscles before and after application of UD-CG 115 BS (200 microM) at an experimental temperature of 21 degrees C. By means of the shortening method, the initial heat was subdivided into the activation heat, which is associated with the calcium turnover, and the tension-dependent heat, which represents the ATP splitting by contractile proteins. The activation heat increased slightly but not significantly from 0.24 +/- 0.05 to 0.34 +/- 0.09 mcal/g. The increase in the tension-dependent heat (from 0.23 +/- 0.07 to 0.49 +/- 0.22 mcal/g) was directly proportional to the increase in the developed stress-time integral (from 0.95 +/- 0.24 to 2.37 +/- 0.76 g.s/mm2). The data indicate that the economy of force generation by contractile proteins is unchanged by UD-CG 115 BS, whereas the activation heat may be slightly increased by this compound. A comparison of UD-CG 115 BS with other substances like isoproterenol or classic phosphodiesterase inhibitors reveals that UD-CG 115 BS increases myocardial force in a more economical way that may have clinical implications. The mode of action of this compound is attributed to its calcium-sensitizing effect on the contractile proteins.

Animals↗

PubMed1989

Effects of pimobendan on hemodynamics and myocardial energetics in patients with idiopathic dilated cardiomyopathy: comparison with nitroprusside.

The influence of pimobendan and nitroprusside on hemodynamics was investigated in nine patients with idiopathic dilated cardiomyopathy (NYHA class II-III). Pimobendan and nitroprusside resulted in a comparable decrease of left ventricular end-diastolic wall stress (preload) by 46% (p less than 0.01) and 52% (p less than 0.01), respectively, and of end-systolic wall stress (afterload) by 36% (p less than 0.01) and 34% (p less than 0.01), respectively. Cardiac index increased from 3.2 +/- 0.4 to 4.2 +/- 0.8 L/min/m2 with pimobendan (p less than 0.01) and did not significantly change with nitroprusside (3.0 +/- 0.6 L/min/m2). Compared to nitroprusside, pimobendan resulted in a significant increase in stroke volume index by 37% (p less than 0.01) and maximum rate of left ventricular pressure rise by 23% (p less than 0.05). Heart rate did not significantly change with either drug. Following the application of pimobendan, there was a decrease in myocardial oxygen consumption from 14.3 +/- 5.1 to 10.6 +/- 3.8 ml/min/100 g (p less than 0.05). The ratio of myocardial oxygen consumption and systolic stress-time integral did not significantly change. Thus, in comparison with nitroprusside, pimobendan exhibits significant inotropic and vasodilating properties. The hemodynamic actions of pimobendan are associated with favorable effects on myocardial energetics.

Adult↗

PubMed1989

Influence of enoximone on mechanics and energetics of right ventricular guinea pig papillary muscles.

Using highly sensitive antimony-bismuth thermopiles, the heat that is liberated during isometric contraction (initial heat) was measured simultaneously with the force signal in right ventricular papillary muscles of guinea pigs (n = 10). Measurements were taken before and after application of enoximone in a concentration of 10(-5) M. Enoximone increased peak developed tension from 1.92 +/- 0.98 to 2.81 +/- 1.11 g/mm2 (p less than 0.01) and the tension-time integral from 1.52 +/- 0.87 to 1.86 +/- 0.86 g.s/mm2 (p less than 0.05). Initial heat was increased from 0.50 +/- 0.13 to 0.79 +/- 0.24 mcal/g (p less than 0.01). The ratio between initial heat and tension-time integral, which is an inverse measure of myocardial economy of force generation, was increased from 3.77 +/- 1.17 to 4.66 +/- 1.49 mucal/g.s.cm (p less than 0.05). To study the potential changes induced by enoximone on an intracellular level, the initial heat was separated into tension-dependent heat (cross-bridge cycling) and tension-independent heat (calcium cycling). The latter increased from 0.20 +/- 0.05 to 0.28 +/- 0.09 mcal/g (p less than 0.05). The tension-dependent heat as normalized for a unit of developed tension-time integral increased from 2.17 +/- 0.63 to 2.86 +/- 0.79 mucal/g.s.cm (p less than 0.01). From these data, we conclude that enoximone decreases the economy of myocardial force generation by (a) increasing the number of calcium ions cycling during one twitch and (b) by altering the fundamental mechanisms of the contractile proteins with respect to force generation, i.e., faster contraction velocity and decreased economy of force generation.

Animals↗