Myocardial energetics and clinical response to the cardiotonic agent MDL 17043 in advanced heart failure

Jack L. Martin, Mariell J. Likoff, Joseph S. Janicki, Warren K. Laskey, John W. Hirshfeld, Karl Weber

Research output: Contribution to journalArticle

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Abstract

Cardiotonic agents may prove useful in the long-term treatment of chronic heart failure provided myocardial efficiency is enhanced and clinical status is improved. Accordingly, the short-term hemodynamic and clinical response to the phosphodiesterase inhibitor, MDL 17043, was evaluated. Intravenous increments of 0.05 mg/kg (maximal total 3 mg/kg) were given to a peak cardiac output response in 13 patients with New York Heart Association functional class IV heart failure secondary to ischemic or myopathic disease. Significant (p < 0.05) responses at peak effect (1.7 mg/kg) included an increase in cardiac output (3.5 to 4.6 liters/min) and heart rate (86 to 90 beats/min) and a decrease in pulmonary capillary wedge (25 to 17 mm Hg), mean arterial (85 to 78 mm Hg) and right atrial (10 to 7 mm Hg) pressures. Coronary sinus flow (measured in nine patients) increased (122 to 144 ml/min, p < 0.01) as did myocardial oxygen uptake (14.1 to 15.1 ml/min, p < 0.01), whereas myocardial extraction of oxygen (78 to 72%, p < 0.01) and lactate (24 to 9%, p < 0.01) decreased with three patients producing lactate at the time of their peak cardiac output response. Nine of the 12 patients given longterm oral therapy improved at least one functional class at 2 weeks. This improvement was sustained at 20 weeks in five patients. Thus, MDL 17043 acutely improves the function of the failing heart. However, the decrease in oxygen extraction occurring with increased myocardial oxygen uptake suggests that intracoronary shunting may occur along with an increase in oxygen demand and contribute to myocardial anaerobiosis in some patients. Hence, to assure an optimal response in myocardial energetics to MDL 17043, individual dose titration and hemodynamic monitoring are recommended.

Original languageEnglish (US)
Pages (from-to)875-883
Number of pages9
JournalJournal of the American College of Cardiology
Volume4
Issue number5
DOIs
StatePublished - Jan 1 1984
Externally publishedYes

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Enoximone
Cardiotonic Agents
Heart Failure
Oxygen
Cardiac Output
Lactic Acid
Hemodynamics
Anaerobiosis
Phosphodiesterase Inhibitors
Coronary Sinus
Heart Rate
Pressure
Lung
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Myocardial energetics and clinical response to the cardiotonic agent MDL 17043 in advanced heart failure. / Martin, Jack L.; Likoff, Mariell J.; Janicki, Joseph S.; Laskey, Warren K.; Hirshfeld, John W.; Weber, Karl.

In: Journal of the American College of Cardiology, Vol. 4, No. 5, 01.01.1984, p. 875-883.

Research output: Contribution to journalArticle

Martin, Jack L. ; Likoff, Mariell J. ; Janicki, Joseph S. ; Laskey, Warren K. ; Hirshfeld, John W. ; Weber, Karl. / Myocardial energetics and clinical response to the cardiotonic agent MDL 17043 in advanced heart failure. In: Journal of the American College of Cardiology. 1984 ; Vol. 4, No. 5. pp. 875-883.
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abstract = "Cardiotonic agents may prove useful in the long-term treatment of chronic heart failure provided myocardial efficiency is enhanced and clinical status is improved. Accordingly, the short-term hemodynamic and clinical response to the phosphodiesterase inhibitor, MDL 17043, was evaluated. Intravenous increments of 0.05 mg/kg (maximal total 3 mg/kg) were given to a peak cardiac output response in 13 patients with New York Heart Association functional class IV heart failure secondary to ischemic or myopathic disease. Significant (p < 0.05) responses at peak effect (1.7 mg/kg) included an increase in cardiac output (3.5 to 4.6 liters/min) and heart rate (86 to 90 beats/min) and a decrease in pulmonary capillary wedge (25 to 17 mm Hg), mean arterial (85 to 78 mm Hg) and right atrial (10 to 7 mm Hg) pressures. Coronary sinus flow (measured in nine patients) increased (122 to 144 ml/min, p < 0.01) as did myocardial oxygen uptake (14.1 to 15.1 ml/min, p < 0.01), whereas myocardial extraction of oxygen (78 to 72{\%}, p < 0.01) and lactate (24 to 9{\%}, p < 0.01) decreased with three patients producing lactate at the time of their peak cardiac output response. Nine of the 12 patients given longterm oral therapy improved at least one functional class at 2 weeks. This improvement was sustained at 20 weeks in five patients. Thus, MDL 17043 acutely improves the function of the failing heart. However, the decrease in oxygen extraction occurring with increased myocardial oxygen uptake suggests that intracoronary shunting may occur along with an increase in oxygen demand and contribute to myocardial anaerobiosis in some patients. Hence, to assure an optimal response in myocardial energetics to MDL 17043, individual dose titration and hemodynamic monitoring are recommended.",
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