Inhibition of development of abdominal aortic aneurysm by glycolysis restriction.

OBJECTIVE: The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development. METHODS AND RESULTS: Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and -3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl(2) in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells. CONCLUSIONS: This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder.

Bystander-witnessed cardiopulmonary resuscitation by nonfamily is associated with neurologically favorable survival after out-of-hospital cardiac arrest in Miyazaki City District.

BACKGROUND: Bystander intervention in cases of out-of-hospital cardiac arrest (OHCA) is a key factor in bridging the gap between the event and the arrival of emergency health services at the site. This study investigated the implementation rate of bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) and 1-month survival after OHCA in Miyazaki prefecture and Miyazaki city district as well as compared them with those of eight prefectures in the Kyushu-Okinawa region in Japan. In addition, we analyzed prehospital factors associated with survival outcomes in Miyazaki city district. METHODS: We used data from an annual report released by the Fire and Disaster Management Agency of Japan (n = 627,982) and the Utstein reporting database in Miyazaki city district (n = 1,686) from 2015 to 2019. RESULT: Despite having the highest rate of bystander CPR (20.8%), the 1-month survival rate (15.7%) of witnessed OHCA cases of cardiac causes in Miyazaki city district was comparable with that in the eight prefectures between 2015 and 2019. However, rates of survival (10.7%) in Miyazaki prefecture were lower than those in other prefectures. In 1,686 patients with OHCA (74 ± 18 years old, 59% male) from the Utstein reporting database identical to the 5-year study period in Miyazaki city district, binary logistic regression analysis demonstrated that age of the recipient [odds ratio (OR) 0.979, 95% confidential interval (CI) 0.964-0.993, p = 0.004)], witness of the arrest event (OR 7.501, 95% CI 3.229-17.428, p < 0.001), AED implementation (OR 14.852, 95% CI 4.226-52.201, p < 0.001), and return of spontaneous circulation (ROSC) before transport (OR 31.070, 95% CI 16.585-58.208, p < 0.001) predicted the 1-month survival with favorable neurological outcomes. In addition, chest compression at a public place (p < 0.001) and by nonfamily members (p < 0.001) were associated with favorable outcomes (p = 0.015). CONCLUSIONS: We found differences in 1-month survival rates after OHCA in the Kyushu-Okinawa region of Japan. Our results suggest that on-field ROSC with defibrillation performed by nonfamily bystanders who witnessed the event determines 1-month neurological outcomes after OHCA in Miyazaki city district. Continued education of citizens on CPR techniques and better access to AED devices may improve outcomes.

Nitric oxide inhalation prompts weaning from the right ventricular assist device: evaluation under continuous-flow biventricular assistance.

OBJECTIVE: The objective of this study was to investigate the effect of nitric oxide on the recovery of right heart function under global ischemia with a continuous-flow biventricular assist device support. METHODS: Fifteen piglets were divided into three groups: continuous-flow biventricular assist support only (control group), global ischemia with continuous-flow biventricular assist support (ischemia only group), and global ischemia with continuous-flow biventricular assist support plus nitric oxide inhalation (nitric oxide group). Two continuous-flow pumps were used as left and right ventricular assist devices. In the ischemic groups (ischemia only group and nitric oxide group), global ischemia was induced for 30 minutes and followed by a 6-hour reperfusion period; the nonischemic control group underwent a 6-hour perfusion period only. The left ventricular assist device was driven at a flow rate of more than 75 to 80 mL/(min. kg). The right ventricular assist device was driven so as to sustain the left ventricular assist device flow, and the animal was weaned from it in accordance with the objective of cardiac recovery. RESULTS: Mean pulmonary arterial pressure remained low in the nitric oxide group (mean 23 mm Hg), whereas it rose from 19.9 mm Hg to 39.3 mm Hg in the ischemia group and to 26.2 mm Hg in the control group. Mixed venous saturation was maintained at more than 60% in all cases. Although no piglets in the ischemia group were able to survive without continuous-flow biventricular assist support, the right ventricular assist device flow ratio (device flow/total systemic flow) in the nitric oxide group could be reduced in all cases, and it was possible to wean the piglets from right ventricular assist device support in 4 of 5 cases. CONCLUSION: Inhalation of 40-ppm nitric oxide enabled smoother maintenance of the left ventricular assist device flow and prompted the weaning from right ventricular assist device support on continuous-flow biventricular assist.

Emergent coronary artery bypass grafting after a broken Rotablator drive-shaft.

A 75-year-old man, who presented with acute myocardial infarction and cardiogenic shock underwent emergency cardiac catheterization, assisted by catecholamine administration, respiratory support with intubation and intra-aortic balloon pumping (IABP). The coronary arteriogram showed a high-grade obstruction of two main branches of the left coronary artery. The occlusion of the left anterior descending coronary artery required immediate treatment. As it was heavily calcified, the cardiologists were forced to use Rotablator®, but the device became stuck and the drive-shaft broke. An emergency coronary artery bypass grafting (CABG) with left internal thoracic artery and saphenous vein graft and mitral valve annuloplasty was performed successfully. The patient was weaned off IABP on the fourth postoperative day, and a defibrillator was implanted on the 81st postoperative day because of heart failure. After these procedures, his general state improved gradually and he was able to leave the hospital, walking alone on the 101st postoperative day. Various reports have appeared describing residual foreign bodies in coronary arteries, and almost 90% of these cases can be dealt with by intravascular procedures, but some need removal by open-chest surgery. An early decision by the cardiologists to go to surgery is recommended to save lives. There has been no previous report of emergent CABG after a stuck Rotablator® tip due to a 'broken drive-shaft'. However, because damage is possible even with reliable devices, there should be no hesitation converting to open-heart surgery in such cases.