Incidence and predictors of pacemaker implantation at follow-up after reversible high-degree sinus node dysfunction or atrioventricular block.

BACKGROUND: A pacemaker implantation is not indicated in cases of reversible high-degree symptomatic sinus node dysfunction (SND) and atrioventricular block (AVB). However, it remains uncertain whether these reversible automaticity/conduction disorders may recur in some patients at follow-up, in the absence of reversible cause. This retrospective study aimed to determine the incidence and predictive factors of permanent pacemaker (PPM) implantation at follow-up and after reversible high-degree SND/AVB. METHODS: Based on medical electronic files codes, we identified patients who were hospitalized in our cardiac intensive care unit between January 2003 and December 2020 due to reversible high-degree SND/AVB and who were discharged from the hospital alive and without PPM implantation. Acute myocardial infarction and post-cardiac surgery patients were excluded. We categorized the patients according to the need for PPM at follow-up due to non-reversible high-degree SND/AVB. RESULTS: Of the 93 patients included, 26 patients (28%) were readmitted for PPM implantation at follow-up after hospital discharge. Among baseline characteristics, compared with patients who did not have high-degree SND/AVB recurrence, those who had subsequent PPM implantation had less frequent previous hypertension (70% vs. 46%, p = .031). Regarding the initial causes of reversible SND/AVB, isolated hyperkalemia was found more often in the patients readmitted for PPM (19% vs. 3% vs. p = .017). Moreover, recurrence of high-degree SND/AVB was significantly associated with the presence of intraventricular conduction disorders (either bundle branch block or left bundle branch hemiblock) on ECG at discharge (36% in patients without PPM vs. 68% in PPM patients, p = .012). CONCLUSION: Almost one third of the patients discharged alive from the hospital after a reversible high-degree SND/AVB needed a pacemaker implantation at follow-up. Complete bundle branch block or left bundle branch hemiblock on discharge ECG after recovery of atrioventricular conduction and/or sinus automaticity was associated with a greater risk of recurrence leading to pacemaker implantation.

Development of abdominal aortic aneurysm is decreased in mice with plasma phospholipid transfer protein deficiency.

Plasma phospholipid transfer protein (PLTP) increases the circulating levels of proatherogenic lipoproteins, accelerates blood coagulation, and modulates inflammation. The role of PLTP in the development of abdominal aortic aneurysm (AAA) was investigated by using either a combination of mechanical and elastase injury at one site of mouse aorta (elastase model) or continuous infusion of angiotensin II in hyperlipidemic ApoE-knockout mice (Ang II model). With the elastase model, complete PLTP deficiency was associated with a significantly lower incidence and a lesser degree of AAA expansion. With the Ang II model, findings were consistent with those in the elastase model, with a lower severity grade in PLTP-deficient mice, an intermediate phenotype in PLTP-deficient heterozygotes, and a blunted effect of the PLTP-deficient trait when restricted to bone marrow-derived immune cells. The protective effect of whole-body PLTP deficiency in AAA was illustrated further by a lesser degree of adventitia expansion, reduced elastin degradation, fewer recruited macrophages, and less smooth muscle cell depletion in PLTP-deficient than in wild-type mice, as evident from comparative microscopic analysis of aorta sections. Finally, cumulative evidence supports the association of PLTP deficiency with reduced expression and activity levels of matrix metalloproteinases, known to degrade elastin and collagen. We conclude that PLTP can play a significant role in the pathophysiology of AAA.

Postnatal overfeeding in rodents by litter size reduction induces major short- and long-term pathophysiological consequences.

Numerous studies have demonstrated that the early postnatal environment can influence body weight and energy homeostasis into adulthood. Rodents raised in small litters have been shown to be a useful experimental model to study the short- and long-term consequences of early overnutrition, which can lead to modifications not only in body weight but also of several metabolic features. Postnatal overfeeding (PNOF) induces early malprogramming of the hypothalamic system, inducing acquired persisting central leptin and insulin resistance and an increase in orexigenic signals. Visceral white adipose tissue, lipogenic activity, and inflammatory status are increased in PNOF rodents, while brown adipose tissue shows reduced thermogenic activity. Pancreatic and hepatic glucose responsiveness is persistently reduced in PNOF rodents, which also frequently present disturbances in plasma lipids. PNOF rodents present increased circulating concentrations of leptin, elevated corticosterone secretion, and significant changes in glucocorticoid sensitivity. PNOF also influences nephrogenesis and renal maturation. Increased oxidative stress is also described in circulating blood and in some tissues, such as the heart or liver. At the cardiovascular level, a moderate increase in arterial blood pressure is sometimes observed and rapid cardiac hypertrophy is observed at weaning; however, during maturation, impaired contractility and fibrosis are observed. Myocardial genome expression is rapidly modified in overfed mice. Moreover, hearts of PNOF rodents are more sensitive to ischemia-reperfusion injury. Together, these results suggest that the nutritional state in the immediate postnatal period should be taken into account, because it may have an impact on cardiometabolic risk in adulthood.

Postnatal overfeeding causes early shifts in gene expression in the heart and long-term alterations in cardiometabolic and oxidative parameters.

BACKGROUND: Postnatal overfeeding (OF) in rodents induces a permanent moderate increase in body weight in adulthood. However, the repercussions of postnatal OF on cardiac gene expression, cardiac metabolism and nitro-oxidative stress are less well known. METHODOLOGY/PRINCIPAL FINDINGS: Immediately after birth, litters of C57BL/6 mice were either maintained at 10 (normal-fed group, NF), or reduced to 3 in order to induce OF. At weaning, mice of both groups received a standard diet. The cardiac gene expression profile was determined at weaning and cardiac metabolism and oxidative stress were assessed at 7 months. The cardiac expression of several genes, including members of the extracellular matrix and apelin pathway, was modified in juvenile OF mice. In adult mice, OF led to an increase in body weight (+30%) and to significant increases in plasma cholesterol, insulin and leptin levels. Myocardial oxidative stress, SOD and catalase activity and mRNA expression were increased in OF mice. In vivo, diastolic and systolic blood pressures were significantly higher and LV shortening and ejection fraction were decreased in OF mice. Ex vivo, after 30 min of ischemia, hearts isolated from OF mice showed lower functional recovery and larger infarct size (31% vs. 54%, p<0.05). Increases in collagen deposition and expression/activity of matrix-metalloproteinase-2 were observed in adult OF mouse hearts. Moreover, an increase in the expression of SOCS-3 and a decrease in STAT-3 phosphorylation were observed in ventricular tissues from OF mice. CONCLUSIONS/SIGNIFICANCE: Our study emphasizes that over-nutrition during the immediate postnatal period in mice leads to early changes in cardiac gene expression, which may permanently modify the heart's structural organization and metabolism and could contribute to a greater susceptibility to myocardial ischemia-reperfusion injury.

Postnatal overfeeding in rats leads to moderate overweight and to cardiometabolic and oxidative alterations in adulthood.

In contrast to the masses of data on obesity, few data are available concerning the cardiometabolic and oxidative consequences of moderate overweight. The model of postnatal overfeeding (OF) induces an increase in body weight at weaning that remains during adult life. Litters of Wistar rats were either maintained at 12 pups (normal-fed group, NF), or reduced to 3 pups at birth in order to induce OF. At 6 months of age, metabolic parameters, circulating oxidative stress and aortic and coronary vasoreactivity were assessed. Cardiac susceptibility to ischemia-reperfusion injury was also evaluated ex vivo as were markers of cardiac remodeling. OF led to an increase in body weight at weaning (+50%); the increase in body weight persisted throughout adult life, but was less marked (+10%). Significant increases in plasma levels of fasting glucose, insulin and leptin were found in OF rats. An increase in both plasma hydroperoxides and cardiac superoxide dismutase activity and a decrease in plasma ascorbate were found in OF rats. Vasoreactivity was not modified, but ex vivo, after 30 min of ischemia, isolated hearts from OF rats showed lower recovery of coronary flow along with a greater release of LDH. Studies on heart tissues showed an increase in collagen content and increased expression and activity of MMP-2. Our findings show that moderate overweight in adult rats, induced by postnatal overfeeding, leads to both metabolic and oxidative disturbances as well as a higher susceptibility to cardiac injury after ischemia ex vivo, which may be explained, at least in part, by ventricular remodeling.