Pakkam, Madona

AbstractAging is associated with cardiac contractile abnormalities, but the etiology of these contractile deficits is unclear. We hypothesized that cardiac contractile and regulatory protein expression is altered during aging. To investigate this possibility, left ventricular (LV) lysates were prepared from young (6 months) and old (24 months) Fischer344 rats. There are no age‐related changes in SERCA2 expression or phospholamban phosphorylation. Additionally, neither titin isoform expression nor phosphorylation differed. However, there is a significant increase in β‐isoform of the myosin heavy chain (MyHC) expression and phosphorylation of TnI and MyBP‐C during aging. In permeabilized strips of papillary muscle, force and Ca2+ sensitivity are reduced during aging, consistent with the increase in β‐MyHC expression and TnI phosphorylation. However, the increase in MyBP‐C phosphorylation during aging may represent a mechanism to compensate for age‐related contractile deficits. In isolated cardiomyocytes loaded with Fura‐2, the peak of the Ca2+ transient is reduced, but the kinetics of the Ca2+ transient are not altered. Furthermore, the extent of shortening and the rates of both sarcomere shortening and re‐lengthening are reduced. These results demonstrate that aging is associated with changes in contractile and regulatory protein expression and phosphorylation, which affect the mechanical properties of cardiac muscle.

Aging is associated with an increased incidence of cardiac dysfunction. We hypothesized that aging associated changes in cardiac regulatory and contractile proteins produce contractile dysfunction. We assessed regulatory and contractile protein expression as well as contractility in left ventricular cardiac muscle from Fischer F-344 rats at 6-, 18-, and 24-month of age. Age-related changes in the expression of β-MHC as well as the expression and phosphorylation of troponin I (TnI) and cardiac myosin binding C protein (MyBP-C) were assessed by Western blot. Aging was associated with an increase in the expression of β-MHC and the phosphorylation of both TnI at Ser23/24 and MyBP-C. Mechanical properties were assessed in Triton-X permeabilized anterior papillary muscle from the left ventricle from both 6- and 24-month old rats. In papillary muscle of 24-month old rats, there was a decrease in maximum Ca2+ activated force, Ca2+ sensitivity of force and the rate constant for force recovery after quick release (ktr). Additionally, cardiomyocytes were isolated from the left ventricle at 6-, 18-, and 24-month of age using a modified Langendorff system. Cardiomyocytes were then loaded with fura-2 AM to measure cytosolic calcium ([Ca2+]cyt) responses to electrical field stimulation (0.5 Hz). [Ca2+]cyt and contractile (sarcomere length shortening) responses to stimulation were simultaneously measured using an IonOptix system. In older cardiomyocytes, the amplitude of evoked [Ca2+]cyt responses was reduced while there was no difference in the kinetics of the [Ca2+]cyt transient. The extent of sarcomere length shortening as well as the rates of both shortening and relaxation were reduced. These results demonstrate that aging is associated with changes in the expression and phosphorylation of contractile and regulatory proteins, which produce changes in cardiac contractility. Supported by a Mayo CV Prospective Grant (FVB). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background: Diabetes mellitus (DM) is one of the risk factors for acute ischemic stroke, usually leading to poor prognosis. While DM can reduce the effect of intravenous thrombolysis, metformin can have a positive outcome on AIS patients. The outcomes of stroke in diabetic patients receiving metformin is largely unexplored. In the present study we performed a systematic review to assess the effect of metformin on AIS outcomes in diabetic patients. Methods: A systematic review of literature was performed following PRISMA guideline. PubMed, Embase, Scopus and Web of science were used for the literature search. Study outcomes such as modified Rankin Scale (mRS 0-2) at discharge, symptomatic intracranial hemorrhage (sICH) and 90-day mortality were extracted from the full text and analysis were performed to calculate 95% confidence intervals with pooled odds ratio for all the outcomes. Results: Total of six studies were included in the analysis with a total of 5390 patients taking metformin and 6039 patients without metformin. Favorable mRS of 0-2 was significantly higher among patients taking metformin (OR 1.52, 95% CI 1.21:1.93). The mortality rate was significantly lower in metformin group (OR 0.51, 95% CI 0.42:0.61). These results favor the beneficial effect of taking metformin among DM patients with AIS. Conclusion: Overall, chronic use of metformin seems to be beneficial in AIS patients with DM. There is a trend of favorable outcomes of mRS and Mortality, with a non-statistical significance increase of sICH.

Background The comparison of mechanical thrombectomy (MT) outcomes between patients with the hyperdense middle cerebral artery sign (HMCAS) and non-HMCAS is important to evaluate the impact of this radiological finding on treatment efficacy. This meta-analysis aimed to assess the association between HMCAS and clinical outcomes in patients undergoing thrombectomy, comparing the outcomes over non-HMCAS. Methods A systematic literature search was conducted in PubMed, Ovid Embase, Google Scholar, and Cochrane Library to identify studies on MT outcomes for M1 occlusions of HMCAS over non-HMCAS. Inclusion criteria encompassed modified Rankin Scale (mRS) score, mortality, symptomatic intracranial hemorrhage (sICH), and successful recanalization. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). Results The meta-analysis was performed for 5 studies with 724 patients. There was no association found between presence of HMCAS and achieving mRS 0–2 (OR = 0.65, 95% CI: 0.29–1.47; p = .544). Mortality analysis also showed no significant association with presence of HMCAS (OR = 0.78, 95% CI: 0.37–1.65; p = .520). No significant difference in sICH risk (OR = 1.54, 95% CI: 0.24–9.66; p = .646) was found between groups. Recanalization analysis showed a non-significant positive association (OR = 1.23, 95% CI: 0.67–2.28; p = .501). Heterogeneity was observed in all analyses. Conclusion Our findings showed that there is no statistically significant difference in mRS scores, mortality, sICH, and recanalization success rates between the HMCAS and non-HMCAS groups.

Background The Woven EndoBridge (WEB) device is used to treat wide-neck bifurcation aneurysms (WNBAs). We conducted a systematic review and meta-analysis to determine the retreatment rate strategies following aneurysmal recurrence of WEB device treated WNBAs. Methods This study is reported following the PRISMA 2020 guidelines. We conducted a systematic review of the literature using PubMed, Scopus, Embase, and Web of Science. Data were pooled using a random-effects model. We calculated pooled prevalence and corresponding 95% confidence intervals (CI). Results We included 11 studies. The overall retreatment rate was 171/1875 aneurysms (10.3%; 95% CI = 8.3–12.9). Stent-assisted coiling was used to treat 59 aneurysms (36.7%; 95% CI = 26.4–48.5), and flow diverters were used to treat 44 aneurysms (18.7%; 95% CI = 9.9–32.5). Following retreatment, the complete occlusion rate was 57/91 aneurysms (62.8%; 95% CI = 48.2–75.3) and the adequate occlusion rate was 24/91 aneurysms (26.4%; 18.4%–36.4%). The most common aneurysmal recurrence site was the anterior communicating artery (44/136 aneurysms, 32.4%; 95% CI = 25.0–40.7). Conclusions Roughly 10% of WNBAs initially treated with the WEB device will undergo retreatment. Retreatment is an effective strategy for WEB-treated aneurysms, with high rates of adequate and complete occlusion. Future studies should work to identify risk factors for aneurysmal recurrence.