1. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy
- Author
-
Paola Pellegrini, Cecilia Vecoli, Demetrio Ciociaro, M. Ciardetti, William C. Stanley, Antonio L'Abbate, Amalia Gastaldelli, Roberto Testa, Andrea Natali, Danilo Neglia, Fabio A. Recchia, Luca Menichetti, Paolo Marraccini, and Alberto De Caterina
- Subjects
Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Cardiac Catheterization ,Time Factors ,Heart disease ,Physiology ,Cardiomyopathy ,Carbohydrate metabolism ,Fatty Acids, Nonesterified ,Tritium ,Coronary circulation ,Oxygen Consumption ,Stress, Physiological ,Physiology (medical) ,Internal medicine ,Coronary Circulation ,Idiopathic dilated cardiomyopathy ,Medicine ,Humans ,Ventricular Function ,Lactic Acid ,Ventricular remodeling ,Aged ,chemistry.chemical_classification ,Carbon Isotopes ,Ventricular Remodeling ,business.industry ,Myocardium ,Cardiac Pacing, Artificial ,Fatty acid ,Dilated cardiomyopathy ,Middle Aged ,medicine.disease ,Myocardial Contraction ,Oxygen ,medicine.anatomical_structure ,Endocrinology ,Glucose ,chemistry ,Case-Control Studies ,cardiovascular system ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Energy Metabolism ,Oxidation-Reduction ,Oleic Acid - Abstract
Under resting conditions, the failing heart shifts fuel use toward greater glucose and lower free fatty acid (FFA) oxidation. We hypothesized that chronic metabolic abnormalities in patients with dilated cardiomyopathy (DCM) are associated with the absence of the normal increase in myocardial glucose uptake and maintenance of cardiac mechanical efficiency in response to pacing stress. In 10 DCM patients and 6 control subjects, we measured coronary flow by intravascular ultrasonometry and sampled arterial and coronary sinus blood. Myocardial metabolism was determined at baseline, during atrial pacing at 130 beats/min, and at 15 min of recovery by infusion of [3H]oleate and [13C]lactate and measurement of transmyocardial arteriovenous differences of oxygen and metabolites. At baseline, DCM patients showed depressed coronary flow, reduced uptake and oxidation of FFA, and preferential utilization of carbohydrates. During pacing, glucose uptake increased by 106% in control subjects but did not change from baseline in DCM patients. Lactate release increased by 122% in DCM patients but not in control subjects. Cardiac mechanical efficiency in DCM patients was not different compared with control subjects at baseline but was 34% lower during stress. Fatty acid uptake and oxidation did not change with pacing in either group. Our results show that in DCM there is preferential utilization of carbohydrates, which is associated with reduced flow and oxygen consumption at rest and an impaired ability to increase glucose uptake during stress. These metabolic abnormalities might contribute to progressive cardiac deterioration and represent a target for therapeutic strategies aimed at modulating cardiac substrate utilization.
- Published
- 2007