H. W. Heiss

Studies on the regulation of myocardial blood flow in man

SummaryIn a comparative study 11 athletes and 11 untrained students were investigated at rest, of these 6 trained and 5 untrained individuals during exercise as well. Myocardial blood flow was measured by the argon method. Myocardial oxygen consumption, myocardial substrate uptake of glucose, lactate, and free fatty acids and cardiac output were determined by the directFick principle. Exercise was standardized according to 65% of an individuals maximal oxygen uptake (ΔVO2 max). Coronary flow reserve was determined by dipyridamole injections. All measurements were made during hemodynamic and respiratory steady-state conditions with the subject in a supine position.At rest, myocardial blood flow and myocardial oxygen consumption were significantly lower in trained subjects compared to the untrained ones. These differences were more pronounced during heavy exercise. They cannot be explained completely by hemodynamic parameters.-During exercise, myocardial substrate uptake shifted to a predominant lactate uptake of almost 90% of total substrate uptake. Total substrate uptake as well as lactate uptake correlated significantly with myocardial oxygen consumption.-Coronary flow reserve was lower in the trained group.It is concluded that the heart muscle of a trained individual requires less energy at a given work load than in the untrained state.ZusammenfassungIn einer vergleichenden Studie wurden 11 Sportstudenten und 11 untrainierte Studenten in Ruhe koronarphysiologisch untersucht. Bei 6 trainierten und 5 untrainierten Probanden konnten zusätzlich Untersuchungen unter schwerer Körperarbeit durchgeführt werden. Die Myokarddurchblutung wurde mit der Argon-Methode gemessen. Myokardialer Sauerstoffverbrauch, myokardialer Substratumsatz von Glukose, Laktat und freien Fettsäuren sowie das Herzzeitvolumen wurden nach dem direktenFickschen Prinzip ermittelt. Die Ergometerbelastung wurde anhand der Differenz aus maximaler Sauerstoffaufnahme und der Sauerstoffaufnahme in Ruhe standardisiert (65% ΔVO2 max). Die Koronarreserve wurde durch Injektion von Dipyridamol bestimmt. Alle Messungen wurden im hämodynamischen und respiratorischen Steady-state vorgenommen.In Ruhe waren Myokarddurchblutung und myokardialer Sauerstoffverbrauch bei den Trainierten signifikant niedriger als bei den Untrainierten. Dieser Unterschied verstärkte sich noch unter schwerer Körperarbeit. Er ist nicht vollständig durch eine unterschiedliche Hämodynamik zu erklären.—Während schwerer Körperarbeit betrug der Laktatumsatz 90% des gesamten Substratumsatzes. Der Umsatz der drei Substrate sowie der Laktatumsatz allein korrelierten signifikant mit dem myokardialen Sauerstoffverbrauch.—Die Koronarreserve war bei den Trainierten niedriger als bei den Untrainierten.Es wird gefolgert, daß bei gleicher relativer Leistung der Energiebedarf des Herzens bei Trainierten geringer ist als bei Untrainierten.

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

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

SummaryUDCG-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<0.01) and decreased left ventricular end-diastolic wall stress (preload) from 52±21 to 28±18 103 dyn/cm2 (p<0.01) and end-systolic wall stress (afterload) from 201 ± 61 to 129 ± 43 103 dyn/cm2 (p<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<0.01), stroke volume index by 37% (p<0.01) and maximum rate of left ventricular pressure rise by 23% (p<0.05). Heart rate did not significantly change with either drug. Myocardial oxygen consumption per beat decreased by 33% (p<0.05) with UDCG-115 and by 30% (p<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.

Myocardial oxygen consumption and substrate uptake in man during physiological and pathological volume load

It is shown in trained and untrained healthy individuals that the energy requirement of the physiologically hypertrophied heart is lower at rest and even more pronounced during submaximal heavy exercise compared to the non-hypertrophied state. This difference exceeds the changes which could have been anticipated by deviations in hemodynamics and total heart weight. In patients with mild or moderate aortic insufficiency the energy expenditure of the pathologically hypertrophied heart per unit tissue mass is comparable to the non-hypertrophied state at rest or during exercise. It is increased in severe aortic regurgitation or additional myocarditis. The transition from compensation to failure may be associated with a steep decrease of the metabolic and flow reserve of the whole heart.

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.

Myocardial oxygen consumption and substrate uptake in man during physiological and pathological volume load@@@Myokardialer Sauerstoffverbrauch und Substrataufnahme beim Menschen während physiologischer und pathologischer Volumenbelastung

SummaryIt is shown in trained and untrained healthy individuals that the energy requirement of the physiologically hypertrophied heart is lower at rest and even more pronounced during submaximal heavy exercise compared to the non-hypertrophied state. This difference exceeds the changes which could have been anticipated by deviations in hemodynamics and total heart weight. In patients with mild or moderate aortic insufficiency the energy expenditure of the pathologically hypertrophied heart per unit tissue mass is comparable to the non-hypertrophied state at rest or during exercise. It is increased in severe aortic regurgitation or additional myocarditis. The transition from compensation to failure may be associated with a steep decrease of the metabolic and flow reserve of the whole heart.ZusammenfassungEs konnte bei trainierten und untrainierten Probanden gezeigt werden, daß der Energiebedarf des physiologisch hypertrophierten Herzens unter Ruhebedingungen und noch stärker während schwerer submaximaler Körperarbeit im Vergleich zum nicht hypertrophierten Zustand niedriger ist. Dieser Unterschied geht über die Veränderungen hinaus, die aufgrund der unterschiedlichen hämodynamischen Parameter und des Herzgewichtes abzuschätzen waren. Bei Patienten mit gering- oder mittelgradiger Aorteninsiffizienz ist der Energieverbrauch des pathologisch hypertrophierten Herzens pro Gewichtseinheit Herzmuskel unter Ruhebedingungen und während submaximaler, jedoch wesentlich geringerer Belastung vergleichbar mit dem nicht hypertrophierten gesunden Herzen. Er ist vermehrt bei großen Regurgitationsvolumina oder begleitender Myokarditis. Der Übergang vom Kompensationszustand zum Herzversagen kann mit einer starken Einschränkung der metabolischen Reserve und der Koronarreserve des Gesamtherzens verbunden sein.

Energetic Consequences of Pharmacological Therapy in Patients with Myocardial Failure

Reducing ventricular load and increasing the contractile force of the myocardium are fundamental principles in the pharmacological therapy of heart failure. Therapeutic goals are the relief of symptoms and the improvement of the prognosis of the disease. Although most vasodilators and inotropic agents have yielded short-term hemodynamic improvement in congestive heart failure, beneficial effects on prognosis have only been shown for vasodilators [5, 7, 8]. The long-term benefit of inotropic agents is controversial. Moreover, detrimental effects of increased myocardial oxygen consumption due to the inotropic stimulation of the myocardium have recently been discussed [14, 16, 25, 28].