Background —The benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by reperfusion damage. In animal models, adenosine limits reperfusion injury, reducing infarct size and improving ventricular function. The aim of this study was to evaluate the safety and feasibility of adenosine adjunct to primary PTCA in AMI. Methods and Results —Fifty-four AMI patients undergoing primary PTCA were randomized to intracoronary adenosine or saline. The 2 groups were similar for age, sex, and infarct location. Adenosine administration was feasible and well tolerated. PTCA was successful in all patients and resulted in TIMI 3 flow in all patients given adenosine and in 19 given saline ( P <0.05). The no-reflow phenomenon occurred in 1 adenosine patient and in 7 saline patients ( P =0.02). Creatine kinase was lower in the adenosine group, and a Q-wave MI developed in 16 adenosine patients and in 23 saline patients ( P =0.04). Sixty-four percent of dyssynergic segments improved in the adenosine group and 36% in the saline group ( P =0.001). Function worsened in 2% of dyssynergic segments in the adenosine group and in 20% in the saline group ( P =0.0001). Adverse cardiac events occurred in 5 patients in the adenosine group and in 13 patients in the saline group ( P =0.03). Conclusions —Intracoronary adenosine administration is feasible and well tolerated in AMI. Adenosine adjunct to primary PTCA ameliorates flow, prevents the no-reflow phenomenon, improves ventricular function, and is associated with a more favorable clinical course.

A, Stanley WC, Recchia FA. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 293: H3270-H3278, 2007. First published October 5, 2007; doi:10.1152/ajpheart.00887.2007.-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 [ 3 H]oleate and [ 13 C]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. microcirculation FATTY ACIDS provide 60 -90% of the energy necessary to sustain contractile function in the resting fasting state, with the remainder coming from glucose and lactate oxidation. During acute cardiac stress, such as pacing or exercise, the healthy human heart rapidly increases glucose and lactate uptake, with a relative decline in free fatty acid (FFA) uptake (1,3,4,9). Clinical and animal studies have suggested that this response is advantageous: it increases myocardial metabolic efficiency, since carbohydrates are a more efficient substrate than lipids, generating more contractile power for any given rate of myocardial oxygen consumption (MV O 2 ) (20,29,31).Dilated cardiomyopathy (DCM) is often characterized by reduced FFA uptake and oxidation and accelerated glycolysis and glucose oxidation under resting conditions (7,21,31). This metabolic shift may act to optimize the limited oxidative capacity of cardiomyopathic hearts resulting from impairment of mitochondrial function (28) and/or ATP transfer from ...

In the absence of changes in clinical chemical parameters, tumor necrosis factor-alpha, interleukin-6, and acute-phase reactant proteins, these results confirm in a clinical setting the upregulation of endothelial adhesiveness observed in experimental hypercholesterolemia and suggest a direct role for cholesterol in regulating this phenomenon, at least in familial hypercholesterolemia.