Randomized double-blind placebo-controlled trial of perhexiline in heart failure with preserved ejection fraction syndrome.

Recently heart failure with preserved ejection fraction (HFpEF) has emerged as a huge epidemic. Increasing evidence shows the role of energy deficiency in the pathophysiology of HFpEF. In the current study, we hypothesize that the use of metabolic modulator perhexiline would correct myocardial energy deficiency and improve exercise capacity and diastolic abnormalities in patients with this syndrome.

Enhanced efficiency of superoxide dismutase-induced cardioprotection by retrograde intracoronary administration.

OBJECTIVE: We hypothesized that modification of the infusion route may improve the efficiency of superoxide dismutase (SOD)-induced cardioprotection against reperfusion injury. The routes for SOD delivery previously examined were intravenous, via the left atrium, or by a combination of these, all of which can deliver SOD into the ischemic myocardium only after reperfusion. In contrast, retrograde intracoronary infusion may be able to deliver SOD before reperfusion. We investigated the feasibility and efficiency of the retrograde intracoronary infusion of SOD to attenuate reperfusion injury. METHODS AND RESULTS: Lewis rats underwent 30-min left coronary artery occlusion followed by reperfusion for 24 h. Just before reperfusion, CuZn-SOD was administered intravenously (15,000 U/kg, V-SOD group) or by retrograde intracoronary infusion (1500 U/kg, R-SOD group) through a catheter inserted into left cardiac vein via left superior vena cava as we have previously reported. This method has been shown to perfuse the whole left ventricular free walls. Controls for each group were injected with phosphate buffer saline only via the same routes (V-PBS and R-PBS group). The R-SOD group demonstrated significantly preserved left ventricular ejection fraction (LVEF; 71.3+/-1.7% vs. 60.8+/-2.3%, p=0.028), reduced infarct size (23.3+/-2.3% vs. 42.4+/-3.5%, p<0.001), and attenuated polymorphonuclear leukocyte (PMNL) infiltration (11.8+/-0.4 vs. 14.8+/-0.2 10(3)/mm(2), p<0.001) compared to the V-SOD group. The V-SOD group demonstrated significantly improved reflow (64.3+/-2.1% vs. 53.4+/-2.4%, p=0.017) and attenuated PMNL infiltration (14.8+/-0.2 vs. 16.8+/-0.7 10(3)/mm(2), p=0.018) compared to the V-PBS group. CONCLUSION: Retrograde intracoronary infusion is a promising, clinically applicable method to enhance the efficacy of SOD-induced myocardial protection against ischemia-reperfusion injury.