3-nitrotyrosine and Coronary-Stenosis

Adjunctive interventions protect from reperfusion injury during primary percutaneous coronary intervention (PCI), but it is not known whether they are also protective during elective PCI. We sought to assess the efficacy of staccato reperfusion (SR) during PCI.. Thirty seven patients with recent acute coronary syndrome and target lesions of 85-100% were randomized to SR (n=18), consisting of 6 periods of 10-s balloon inflation/deflation (total time, 120 sec) or abrupt reperfusion (AR, n=19), consisting of a single continuous 120-s balloon inflation; subsequently, all underwent stent implantation. Left ventricular wall motion score was echocardiography determined at baseline, 10 days and 1 year later. The oxidative markers malondialdehyde (MDA) and nitrotyrosine were assessed at baseline, 3 and 18 min after PCI. Patients were also followed for 1 year for major events (death, non-fatal myocardial infarction or revascularization).. Wall motion score index (SR: 1.34+/-0.29 (baseline), 1.17+/-0.17 (10-day), 1.08+/-0.12 (1-year); AR: 1.33+/-0.22, 1.27+/-0.20, 1.24+/-0.22, respectively) improved significantly as a result of SR (F=8.951, p=0.002). Similarly, the biomarkers of oxidative injury, MDA (1.74+/-0.49 micromol/L in SR vs. 2.45+/-1.26 micromol/L in AR, p=0.002) and nitrotyrosine (5.23+/-5.58 nmol/L in SR vs. 9.79+/-7.83 nmol/L in AR, p=0.003) measured 18 min after PCI were significantly lower in SR. No major events occurred.. SR can improve long-term wall motion score during PCI, at least partly through the attenuation of a reperfusion-type oxidative injury that also occurs in these patients.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Biomarkers; Coronary Stenosis; Female; Follow-Up Studies; Humans; Male; Malondialdehyde; Middle Aged; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Pilot Projects; Recovery of Function; Secondary Prevention; Stents; Time Factors; Treatment Outcome; Tyrosine; Ultrasonography; Ventricular Function, Left

Coexistence of chronic kidney disease (CKD) and heart failure (HF) in humans is associated with poor outcome. We hypothesized that preexistent CKD worsens cardiac outcome after myocardial infarction, and conversely that ensuing HF worsens progression of CKD. Subtotally nephrectomized (SNX) or sham-operated (CON) rats were subjected to coronary ligation (CL) or sham surgery in week 9 to realize four groups: CON, SNX, CON + CL, and SNX + CL. Blood pressure and renal function were measured in weeks 8, 11, 13, and 15. In week 16, cardiac hemodynamics and end-organ damage were assessed. Blood pressure was significantly lower in SNX + CL vs. SNX. Despite this, glomerulosclerosis was more severe in SNX + CL vs. SNX. Two weeks after CL, SNX + CL had more cardiac dilatation compared with CON + CL (end-diastolic volume index: 0.28 ± 0.04 vs. 0.19 ± 0.03 ml/100 g body wt; mean ± SD, P < 0.001), although infarct size was similar. During follow-up in SNX + CL, ejection fraction declined. Mortality was only observed in SNX + CL (2 out of 9). In SNX + CL, end-diastolic pressure (18 ± 4 mmHg) and tau (29 ± 9 ms), the time constant of active relaxation, were significantly higher compared with SNX (13 ± 3 mmHg, 20 ± 4 ms; P < 0.01) and CON + CL (11 ± 5 mmHg, 17 ± 2 ms; P < 0.01). The diameter of small arterioles in the myocardium was significantly decreased in SNX + CL vs. CON + CL (P < 0.01). Urinary excretion of NO metabolites was significantly lower in SNX + CL compared with both CL and SNX. This study demonstrates the existence of more heart and more kidney damage in a new model of combined CKD and HF than in the individual models. Such enhanced damage appears to be separate from systemic hemodynamic changes. Reduced nitric oxide availability may have played a role in both worsened glomerulosclerosis and cardiac diastolic function and appears to be a connector in the cardiorenal syndrome.

Topics: Animals; Blood Pressure; Cardio-Renal Syndrome; Coronary Stenosis; Disease Models, Animal; Gene Expression; Heart Failure; Ligation; Male; Myocarditis; Nephrectomy; Nephritis; Nitrates; Nitrites; Peptidyl-Dipeptidase A; Prorenin Receptor; Rats; Rats, Inbred Lew; Receptors, Cell Surface; Renal Insufficiency, Chronic; Renin; Thiobarbituric Acid Reactive Substances; Tyrosine; Ultrasonography

The goal of this study was to investigate the role of cardiac nerves on the response to 90-minute coronary artery stenosis (CAS), which reduced coronary blood flow by 40% for 90 minutes, and subsequent myocardial stunning after reperfusion in chronically instrumented conscious pigs. In pigs with regional cardiac denervation (CD), myocardial stunning was intensified, ie, at 12 hours reperfusion wall thickening (WT) was depressed more, P<0.05, in CD (-46+/-5%) as compared with intact pigs (-31+/-3%) and remained depressed in CD at 24 hours reperfusion (-45+/-6%). Although the TTC technique was negative for infarct, histopathological analysis revealed patchy necrosis present in 11+/-2% of the area at risk. In intact pigs, WT had essentially recovered at 24 hours without infarct. In CD pigs treated with either an antioxidant, N-2-mercaptopropionyl glycine (MPG, 100 mg/kg per hour) or systemic nitric oxide synthase inhibition using N(omega)-nitro-L-arginine (L-NA, 30 mg/kg for 3 days), recovery of wall thickening was similar to that in pigs with intact nerves and without evidence of infarct. Immunohistochemistry analysis for 3-nitrotyrosine in tissue after CAS and 1 hour reperfusion demonstrated enhanced peroxynitrite-related protein nitration in pigs with regional CD compared with pigs with intact cardiac nerves, and pigs with regional CD and MPG or L-NA. Thus, reperfusion after myocardial ischemia in the setting of CD results in enhanced stunning and development of infarct. The underlying mechanism appears to involve nitric oxide and reactive oxygen species.

Topics: Animals; Coronary Stenosis; Denervation; Enzyme Inhibitors; Heart; Hemodynamics; Immunohistochemistry; Models, Animal; Myocardial Reperfusion; Myocardial Stunning; Myocardium; Necrosis; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Norepinephrine; Reactive Oxygen Species; Swine; Tyrosine