Do Aging and Parity Affect VEGF-A/VEGFR Content and Signaling in the Ovary?—A Mouse Model Study

In this study, the effects of aging and parity on VEGF-A/VEGFR protein content and signaling in the mice ovaries were determined. The research group consisted of nulliparous (virgins, V) and multiparous (M) mice during late-reproductive (L, 9–12 months) and post-reproductive (P, 15–18 months) stages. Whilst ovarian VEGFR1 and VEGFR2 remained unchanged in all the experimental groups (LM, LV, PM, PV), protein content of VEGF-A and phosphorylated VEGFR2 significantly decreased only in PM ovaries. VEGF-A/VEGFR2-dependent activation of ERK1/2, p38, as well as protein content of cyclin D1, cyclin E1, and Cdc25A were then assessed. In ovaries of LV and LM, all of these downstream effectors were maintained at a comparable low/undetectable level. Conversely, the decrease recorded in PM ovaries did not occur in the PV group, in which the significant increase of kinases and cyclins, as well phosphorylation levels mirrored the trend of the pro-angiogenic markers. Altogether, the present results demonstrated that, in mice, ovarian VEGF-A/VEGFR2 protein content and downstream signaling can be modulated in an age- and parity-dependent manner. Moreover, the lowest levels of pro-angiogenic and cell cycle progression markers detected in PM mouse ovaries sustains the hypothesis that parity could exert a protective role by downregulating the protein content of key mediators of pathological angiogenesis

Endocannabinoid System Components of the Female Mouse Reproductive Tract Are Modulated during Reproductive Aging

The endocannabinoid (eCB) system has gained ground as a key modulator of several female fertility-related processes, under physiological/pathological conditions. Nevertheless, its modulation during reproductive aging remains unclear. This study aimed to investigate the expression levels of the main receptors (cannabinoid receptor 1,CB1; cannabinoid receptor 2, CB2; G-protein coupled receptor, GPR55; and transient receptor potential vanilloid type 1 channel, TRPV1) and metabolic enzymes (N-acylphosphatidylethanolamine phospholipase D, NAPE-PLD; fatty acid amide hydrolase, FAAH; monoacylglycerol lipase, MAGL; and diacylglycerol lipase, DAGL-α and -β) of this system in the ovaries, oviducts, and uteri of mice at prepubertal, adult, late reproductive, and post-reproductive stages through quantitative ELISA and immunohistochemistry. The ELISA showed that among the receptors, TRPV1 had the highest expression and significantly increased during aging. Among the enzymes, NAPE-PLD, FAAH, and DAGL-β were the most expressed in these organs at all ages, and increased age-dependently. Immunohistochemistry revealed that, regardless of age, NAPE-PLD and FAAH were mainly found in the epithelial cells facing the lumen of the oviduct and uteri. Moreover, in ovaries, NAPE-PLD was predominant in the granulosa cells, while FAAH was sparse in the stromal compartment. Of note, the age-dependent increase in TRPV1 and DAGL-β could be indicative of increased inflammation, while that of NAPE-PLD and FAAH could suggest the need to tightly control the levels of the eCB anandamide at late reproductive age. These findings offer new insights into the role of the eCB system in female reproduction, with potential for therapeutic exploitation

How should I wean my next intra-aortic balloon pump? Differences between progressive volume weaning and rate weaning.

OBJECTIVE: Although the intra-aortic balloon pump is the most used ventricular assist device, no study has ever evaluated the best weaning method. We compared 2 different intra-aortic balloon pump weaning methods.METHODS: Thirty consecutive patients needing an intra-aortic balloon pump because of perioperative low-output cardiac syndrome were randomized to be weaned by ratio (4 consecutive hours of a 1:2 assisting ratio followed by 1 hour of a 1:3 ratio; group R) or by progressive volume deflation (10% of total volume every hour for 5 consecutive hours; 15 patients, group V). A duration of 5 hours was set a priori as the weaning duration. The weaning protocol was started when the cardiac index was greater than 2.5 L/min/m(2), the central venous pressure was 12 mm Hg or less, the blood lactate was less than 2.5 mmol/L, the mean arterial pressure was greater than 65 mm Hg, and the preserved urine output (≥1 mL/kg/hr) lasted for at least 5 consecutive hours before weaning. The cardiac index, indexed systemic vascular resistance, cardiac cycle efficiency, and central venous pressure were registered at 9 points (T0, start; T1 to T5, the first 5 weaning hours; T6, 2 hours after withdrawal; T7, 12 hours after withdrawal; and T8, at intensive care unit discharge) using the pressure recording analytical method. The interval from intra-aortic balloon pump withdrawal to intensive care unit discharge, weaning failure, perioperative troponin I, and lactate (same points) were compared.RESULTS: All patients, except for 1 belonging to group R (P = 1.0), were successfully weaned. Group V had better preserved cardiac index, indexed systemic vascular resistance, cardiac cycle efficiency, and central venous pressure (group*time P = .0001). Group R had worse cardiac index from T5 to T8 (P ≤ .0001), indexed systemic vascular resistance from T2 to T8 (P ≤ .004), cardiac cycle efficiency from T3 to T8 (P ≤ .001), central venous pressure from T4 to T8 (P ≤ .0001), and a longer interval from intra-aortic balloon pump withdrawal to intensive care unit discharge (P = .0001). The lactate level was lower in group V from T5 to T8 (P ≤ .027; group*time P = .001).CONCLUSIONS: Intra-aortic balloon pump weaning by volume deflation allowed better hemodynamic and metabolic parameters

Orthotopic heart transplantation with bicaval anastomosis using older donors

Non randomized study of myocardial protection using blood cardioplegia during HT

Dorsal extradural meningioma: Case report and literature review

Extradural spinal mass lesions are most commonly metastatic tumors. Extradural meningiomas are rare, accounting for approximately 2.5-3.5% of spinal meningiomas; intraoperatively, they are easily mistaken for malignant tumors, especially in the en plaque variety, resulting in inadequate surgical treatment

Myocardial Protection in Heart Transplantation Using Blood Cardioplegia: 12 Years Outcome of a Prospective Randomized Trial

BACKGROUND: Blood cardioplegia yields a lower prevalence of right heart failure, arrhythmias, and myocardial ischemia early after heart transplantation (HTx). Because depolarizing (high [K(+)]) cardioplegic solutions may alledgedly cause endothelial damage, the 12-year outcome of a prospective randomized trial was reviewed. METHODS: Between January 1997 and March 1998, 47 consecutive patients received crystalloid (Group 1, n = 27) or blood cardioplegia (Group 2, n = 20). The groups were similarly matched: recipient age (54 ± 11 vs 55 ± 7 years, p = 0.9), sex (89% vs 90% males, p = 0.9), diagnosis (63% vs 65% dilated cardiomyopathy, p = 0.8), elevated (>4 WU) pulmonary vascular resistance (30% vs 30%, p = 0.9), prior operations (22% vs 30%, p = 0.5), urgent HTx (7% vs 20%, p = 0.2), donor age (32 ± 11 vs 31 ± 13 years, p = 0.7), donor sex (78% vs 70% males, p = 0.5), donor cause of death (33% vs 40% vascular, p = 0.5), and global myocardial ischemia (176 ± 51 vs 180 ± 58 minutes p = 0.5). Hemodynamically unstable donors were more prevalent in Group 2 (15% vs 45%, p = 0.02). The 45 hospital survivors underwent yearly echocardiography, coronary angiography, and coronary intravascular ultrasound (IVUS) imaging during follow-up. RESULTS: During follow-up (10.4 ± 5.2, range, 0.9-12.7 years), Groups 1 and 2 had comparable mortality (46% vs 42%, p = 0.7) and cause of death (chronic rejection: 50% vs 50%; neoplasia: 33% vs 25%, p = 0.8). Survival at 12 years was 50% ± 12% vs 52% ± 11% (p = 0.9). Follow-up echocardiogram showed similar mean left ventricular ejection fraction (LVEF; 47% ± 12% vs 49% ± 11%, p = 0.7) and prevalence of LVEF 0.5 mm) in the proximal and distal left anterior descending artery (67% vs 40%; 58% vs 45%) and higher number of percutaneous coronary interventions (2.7 ± 0.5 vs 1.8 ± 0.3, p = 0.3) was noted in Group 1. CONCLUSIONS: Use of blood cardioplegia is safe and results in comparable survival and prevalence of adverse events late after HTx. The trend towards greater freedom from chronic rejection and more limited extent of coronary artery disease in grafts protected with blood cardioplegia awaits confirmation

Blood versus crystalloid cardioplegia for myocardial protection of donor hearts during transplantation: a prospective, randomized clinical trial

AbstractObjective: To assess the safety and efficacy of myocardial protection of the donor heart during transplantation with the use of blood cardioplegia, a prospective randomized clinical trial was undertaken between January 1997 and March 1998. Methods: Forty-seven consecutive patients were assigned either to crystalloid (27 patients; group 1) or blood cardioplegia (20 patients; group 2). Comparison of recipient age (54 ± 11 years vs 55 ± 7 years; P = .9), sex (89% vs 90% male patients; P = .9), diagnosis (63% vs 65% dilated cardiomyopathy; P = .8), elevated pulmonary vascular resistance (30% vs 30%; P = .9), prior cardiac operations (22% vs 30%; P = .5), need for urgent heart transplantation (7% vs 20%; P = .2), donor age (32 ± 11 years vs 31 ± 13 years; P = .7), cause of death (33% vs 40% vascular; P = .5), and global myocardial ischemia (176 ± 51 minutes vs 180 ± 58 minutes; P = .5) showed no difference. Hemodynamically unstable donors (15% vs 45%; P = .02) were more prevalent in group 2. Results: Operative mortality rates (4% vs 5%; P = .8), high-dose inotropic support (41% vs 30%; P = 0.6), and postoperative mechanical assistance (11% vs 10%; P = 0.9) were comparable in the 2 groups. Prevalence of acute right heart failure (27% vs 0; P = .02) and of temporary complete atrioventricular block (52% vs 20%; P = .02) were greater in group 1. Spontaneous sinus rhythm recovery was more prevalent in group 2 (11% vs 40%; P = .02). Higher peak creatine kinase (1429 ± 725 u/L vs 868 ± 466 u/L; P = .01) and creatine kinase MB (144 ± 90 u/L vs 102 ± 59 u/L; P = .06) levels suggested more severe ischemic injury in group I. Conclusion: Use of blood cardioplegia was associated with a lower prevalence of right heart failure, cardiac rhythm dysfunction, and laboratory evidence of ischemia. (J Thorac Cardiovasc Surg 1999;118:787-95