The incidence of heart failure (HF) is increasing and is associated with a poor prognosis. Moreover, HF often coexists with renal dysfunction and is associated with a worsened outcome. In many experimental studies on cardiac dysfunction, the function of other organs was either not addressed or did not show any decline. Until now, the exact mechanisms for initiating and sustaining this interaction are still unknown. The objective of this study is to use volume overload to induce cardiac hypertrophy and HF in aortocaval fistula (ACF) rat models, and to elucidate how volume overload affects metabolic changes in the kidney, even with normal renal function, in HF. The results showed the metabolic changes between control and ACF rats, including taurine metabolism; purine metabolism; glycine, serine, and threonine metabolism; glycerophospholipid metabolism; and histidine metabolism. Increasing the downstream purine metabolism from inosine to uric acid in the kidneys of ACF rats induced oxidative stress through xanthine oxidase. This result was consistent with HK-2 cells treated with xanthine and xanthine oxidase. Under oxidative stress, taurine accumulation was observed in ACF rats, indicating increased activity of the hypotaurine–taurine pathway as a defense mechanism against oxidative stress in the kidney. Another antioxidant, ascorbic acid 2-sulfate, showed lower levels in ACF rats, indicating that the kidneys experience elevated oxidative stress due to volume overload and HF. In summary, metabolic profiles are more sensitive than clinical parameters in reacting to damage to the kidney in HF.
Matrix metalloproteinase (MMP) plays an important role in the pathogenesis of atrial fibrillation (AF). The MMP9 promoter has a functional polymorphism rs3918242 that can regulate the level of gene transcription. This study recruited 200 AF patients and 240 controls. The MMP9 rs3918242 was examined by polymerase chain reactions. HL-1 atrial myocytes were cultured and electrically stimulated. Right atrial appendages were obtained from six patients with AF and three controls with sinus rhythm undergoing open heart surgery. The MMP9 expression and activity were determined using immunohistochemical analysis and gelatin zymography, respectively. Rapid pacing induces MMP9 secretion from HL-1 myocytes in a time- and dose-dependent manner. The responsiveness of MMP9 transcriptional activity to tachypacing was significantly enhanced by rs3918242. The expression of MMP9 was increased in fibrillating atrial tissue than in sinus rhythm. However, the distribution of rs3918242 genotypes and allele frequencies did not significantly differ between the control and AF groups. HL-1 myocyte may secrete MMP9 in response to rapid pacing, and the secretion could be modulated by rs3918242. Although the MMP9 expression of human atrial myocyte is associated with AF, our study did not support the association of susceptibility to AF among Taiwanese subjects with the MMP9 rs3918242 polymorphism.
Background. The optimal percutaneous coronary intervention (PCI) strategy and clinical outcomes of long lesions with an extremely small residual lumen remain unclear. This study aimed to assess the efficacy of a modified stenting strategy for diffuse coronary artery disease (CAD) with an extremely small distal residual lumen. Methods. 736 Patients who received PCI using second-generation drug-eluting stents (DES) ≥38 mm long were retrospectively included and categorized into an extremely small distal vessel (ESDV) group (≤2.0 mm) and a non-ESDV group (>2.0 mm) according to the maximal luminal diameter of the distal vessel (dsDMax). A modified stenting technique was applied by landing an oversized DES in the distal segment with the largest luminal diameter and maintaining the distal stent edge partially expanded. Results. The mean dsDMax and stent lengths were 1.7 ± 0.3 mm and 62.6 ± 18.1 mm in the ESDV group and 2.7 ± 0.5 mm and 59.1 ± 16.0 mm in non-ESDV groups, respectively. The acute procedural success rate was high in both the ESDV and non-ESDV groups (95.8% and 96.5%, p = 0.70) with rare distal dissection (0.3% and 0.5%, p = 1.00). The target vessel failure (TVF) rate was 16.3% in the ESDV group and 12.1% in the non-ESDV group at a median follow-up of 65 months without significant differences after propensity score matching. Conclusions. PCI using contemporary DES with this modified stenting technique is effective and safe for diffuse CAD with extremely small distal vessels.