Showing papers by "Salvatore Pepe published in 1999"
TL;DR: Manipulating the cardiac Mito membrane n-3-to-n-6 PUFA ratio shows that the activation of Ca2+-dependent PDH can be augmented when the n-4 to n-6PUFA ratio is low, or attenuated when this ratio is relatively high (n-3 PUFA-rich diet).
Abstract: Aberrations in cell Ca2+ homeostasis have been known to parallel both changes in membrane lipid composition and aging. Previous work has shown that the lowered efficiency of work performance, which...
161 citations
TL;DR: Compared to younger counterparts, the senescent myocardium of rats and humans has a reduced capacity to tolerate ischemic or aerobic stress and recover pre‐stress contractile performance, however, this reduction is attenuated by CoQ10 pretreatment.
Abstract: The inferior recovery of cardiac function after interventional cardiac procedures in elderly patients compared to younger patients suggests that the aged myocardium is more sensitive to stress. We report two studies that demonstrate an age-related deficit in myocardial performance after aerobic and ischemic stress and the capacity of CoQ10 treatment to correct age-specific diminished recovery of function. In Study 1 the functional recovery of young (4 mo) and senescent (35 mo) isolated working rat hearts after aerobic stress produced by rapid electrical pacing was examined. After pacing, the senescent hearts, compared to young, showed reduced recovery of pre-stress work performance. CoQ10 pretreatment (daily intraperitoneal injections of 4 mg/kg CoQ10 for 6 weeks) in senescent hearts improved their recovery to match that of young hearts. Study 2 tested whether the capacity of human atrial trabeculae (obtained during surgery) to recover contractile function, following ischemic stress In vitro (60 min), is decreased with age and whether this decrease can be reversed by CoQ10. Trabeculae from older individuals (≥ 70 yr) showed reduced recovery of developed force after simulated ischemia compared to younger counterparts (<70 yr). Notably, this age-associated effect was prevented in trabeculae pretreated In vitro (30 min at 24°C) with CoQ10 (400 μM). We measured significantly lower CoQ10 content in trabeculae from ≥ 70 yr patients. In vitro pretreatment raised trabecular CoQ10 content to similar levels in all groups. We conclude that, compared to younger counterparts, the senescent myocardium of rats and humans has a reduced capacity to tolerate ischemic or aerobic stress and recover pre-stress contractile performance, however, this reduction is attenuated by CoQ10 pretreatment.
46 citations
TL;DR: In this article, the effect of dietary polyunsaturated fatty acids (PUFAs) upon mitochondrial Ca2+ content and dehydrogenase activation in the rat heart was examined.
Abstract: We have examined the effect of dietary polyunsaturated fatty acids (PUFAs) upon mitochondrial Ca2+ content and dehydrogenase activation in the rat heart. Diets were either a conventional low-fat chow (Ref) or were rich in n-3 PUFAs from fish oils (n-3) or n-6 PUFAs from animal fat (n-6). We found that the n-3 diet minimized the rise in mitochondrial Ca2+ seen in response to positive inotropic intervention with noradrenaline, and also minimized the activation of pyruvate dehydrogenase, which is Ca2+ dependent. As the work output of all three groups of hearts was the same, this observation may explain the previous finding of increased thermodynamic efficiency of the n-3 heart relative to the n-6 heart. When hearts were subjected to low-flow ischaemia (15 min), followed by 5 min of reperfusion, increases of mitochondrial Ca2+ were less in the n-3 group than in the n-6 group. In more prolonged ischaemia and reperfusion, n-3 feeding may confer protection against mitochondrial Ca2+ overload, opening of the permeability transition pore and cell death. Notably, the effects of n-3 feeding on mitochondrial functioning were most apparent in hearts from senescent rats (23 months). This is consistent with our finding that the decrease in mitochondrial membrane cardiolipin content, and increase in phosphatidylcholine, which occurred with aging in the Ref and n-6 groups, was totally prevented by n-3 feeding. Thus there are a number of reasons to regard an n-3-rich diet as being protective of the heart in aging mammals.
25 citations
TL;DR: The results are consistent with the notion that the occurrence of mtDNA deletions during aging is a random process, involving their production throughout the lifetime of an individual, and are superimposed on those already accumulated by propagation and segregation of mutations formed earlier in life.
23 citations