Outcomes after angiography with sodium bicarbonate and acetylcysteine

Background: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy. Methods: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point. Results: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury. Conclusions: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466.

In-Stent Restenosis in Saphenous Vein Grafts (from the DIVA Trial)

Saphenous vein grafts (SVGs) have high rates of in-stent restenosis (ISR). We compared the baseline clinical and angiographic characteristics of patients and lesions that did develop ISR with those who did not develop ISR during a median follow-up of 2.7 years in the DIVA study (NCT01121224). We also examined the ISR types using the Mehran classification. ISR developed in 119 out of the 575 DIVA patients (21%), with similar incidence among patients with drug-eluting stents and bare-metal stents (BMS) (21% vs 21%, p = 0.957). Patients in the ISR group were younger (67 ± 7 vs 69 ± 8 years, p = 0.04) and less likely to have heart failure (27% vs 38%, p = 0.03) and SVG lesions with Thrombolysis In Myocardial Infarction 3 flow before the intervention (77% vs 83%, p <0.01), but had a higher number of target SVG lesions (1.33 ± 0.64 vs 1.16 ± 0.42, p <0.01), more stents implanted in the target SVG lesions (1.52 ± 0.80 vs 1.31 ± 0.66, p <0.01), and longer total stent length (31.37 ± 22.11 vs 25.64 ± 17.42 mm, p = 0.01). The incidence of diffuse ISR was similar in patients who received drug-eluting-stents and BMS (57% vs 54%, p = 0.94), but BMS patients were more likely to develop occlusive restenosis (17% vs 33%, p = 0.05). © 202

Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers

<p>Abstract</p> <p>Background</p> <p>Previous studies on the effects of Statins in preventing atrial fibrillation (AF) after cardiac surgery have shown conflicting results. Whether statins prevent AF in patients treated with postoperative beta blockers and whether the statin-effect is dose related are unknown.</p> <p>Methods</p> <p>We retrospectively studied 1936 consecutive patients who underwent coronary artery bypass graft (CABG) (n = 1493) or valve surgery (n = 443) at the Minneapolis Veterans Affairs Medical Center. All patients were in sinus rhythm before the surgery. Postoperative beta blockers were administered routinely (92% within 24 hours postoperatively).</p> <p>Results</p> <p>Mean age was 66+10 years and 68% of the patients were taking Statins. Postoperative AF occurred in 588 (30%) patients and led to longer length of stay in the intensive care unit versus those without AF (5.1+7.6 days versus 2.5+2.3 days, p < 0.0001). Patients with a past history of AF had a 5 times higher risk of postoperative AF (odds ratio 5.1; 95% confidence interval 3.4 to 7.7; p < 0.0001). AF occurred in 31% of patients taking statins versus 29% of the others (p = 0.49). In multivariable analysis, statins were not associated with AF (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.7 to 1.2; p = 0.59). However, in a subgroup analysis, the patients treated with Simvastatin >20 mg daily had a 36% reduction in the risk of postoperative AF (OR 0.64, 95% CI 0.43 to 0.6; p = 0.03) in comparison to those taking lower dosages.</p> <p>Conclusion</p> <p>Among cardiac surgery patients treated with postoperative beta blockers Statin treatment reduces the incidence of postoperative AF when used at higher dosages</p

Increased activity of the sarcoplasmic reticular calcium pump in porcine stunned myocardium

OBJECTIVE: The aim was to determine whether changes in sarcoplasmic reticular Ca2+ transport activity and the degree of phosphorylation of phospholamban of "stunned" myocardium are involved in the reversible depression of contractile function.METHODS: In anaesthetised open chest swine, stunning was induced by subjecting the myocardium perfused by the left anterior descending coronary artery to two cycles of 10 min of occlusion and 30 min of reperfusion. Before and after stunning, systemic haemodynamic variables and regional myocardial function and perfusion were determined, while biopsies were taken for determination of the content of high energy phosphate compounds. Sarcoplasmic reticular function (ATP dependent Ca2+ transport and phosphorylation of phospholamban) of the stunned and control myocardium was determined at the end of the stunning protocol.RESULTS: In the stunned myocardium the segment length shortening decreased from 17.4(SD 4.0)% to 3.5(4.4)%, while perfusion was 38% less than at baseline. ATP and total adenine nucleotide levels of the stunned myocardium were about 35% lower than in the control myocardium, but the energy charge was normal as creatine phosphate levels had increased by 66% over the content determined at baseline. Ca2+ uptake by the sarcoplasmic reticulum isolated from the stunned region was 17% (p&lt;0.05) higher than Ca2+ uptake from the control region [1240(303) and 1450(280) nmol·min-1·mg-1 protein, respectively]. In the presence of exogenous cyclic AMP dependent protein kinase the amount of 32P incorporated into phospholamban was similar for both myocardial regions.CONCLUSIONS: In this model of stunned porcine myocardium, the phosphorylation state of phospholamban was unchanged, but Ca2+ uptake by the sarcoplasmic reticulum was slightly increased. The results indicate that a change in active Ca2+ transport by the sarcoplasmic reticulum is most likely not to be the principal cause of contractile dysfunction of stunned myocardium.</p

Enhanced gene expression of calcium regulatory proteins in stunned porcine myocardium

OBJECTIVE: Increasing evidence points to a molecular disturbance of Ca2+ homeostasis in stunned myocardium. The aim of this study was therefore to investigate the expression of mRNAs for Ca2+ binding proteins related to the sarcoplasmic reticulum in a porcine model of myocardial stunning.METHODS: In 22 anaesthetised pigs, stunning was achieved by one or two cycles of 10 min left anterior descending coronary artery occlusion and reperfusion. Hearts were excised at various timepoints of the protocol. Total RNA was extracted from stunned (experimental) as well as normally perfused (control) myocardium.RESULTS: Northern blot analysis using radioactive cDNA probes revealed that the Ca(2+)-ATPase mRNA levels increased 1.6-fold compared to the control value at 90 min of the second reperfusion. The steady state level of phospholamban mRNA rose 2.5-fold at 180 min of reperfusion. A 2.3-fold increase in calsequestrin mRNAs was observed after 90 min of the second reperfusion. The calmodulin and alpha, beta myosin heavy chain mRNA levels were unchanged. A glyceraldehyde-3-phosphate dehydrogenase cDNA probe served as a reference system. Nuclear run-on assays showed increased transcription for Ca2+-ATPase and calsequestrin at 90 min of reperfusion, supporting the view that increased mRNA levels seen with northern hybridisation were due to increased transcription of the respective gene.CONCLUSIONS: The results suggest specific repair mechanisms of stunned myocardium and point to the involvement of calcium regulatory proteins related to the sarcoplasmic reticulum in the pathogenesis of myocardial stunning.</p

Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone

Over 240 million non-cardiac operations occur each year and are associated with a 15–20% incidence of adverse perioperative cardiovascular events. Unfortunately, preoperative therapies that have been useful for chronic ischemic heart diseases, such as coronary artery revascularization, antiplatelet agents, and beta-blockers have failed to improve outcomes. In a pre-clinical swine model of ischemic heart disease, we showed that daily administration of ubiquinone (coenzyme Q10, CoQ10) enhances the antioxidant status of mitochondria within chronically ischemic heart tissue, potentially via a PGC1α-dependent mechanism. In a randomized controlled trial, among high-risk patients undergoing elective vascular surgery, we showed that NT Pro-BNP levels are an important means of risk-stratification during the perioperative period and can be lowered with administration of CoQ10 (400 mg/day) for 3 days prior to surgery. The review provides background information for the role of oxidant stress and inflammation during high-risk operations and the potential novel application of ubiquinone as a preoperative antioxidant therapy that might reduce perioperative adverse cardiovascular outcomes

Dobutamine restores the reduced efficiency of energy transfer from total mechanical work to external mechanical work in stunned porcine myocardium

OBJECTIVE: In order to determine whether the relatively high oxygen consumption of stunned myocardium is related to decreased mechanical efficiency, myocardial oxygen consumption (MVo2) and its major determinants were studied in 10 open chest anaesthetised pigs.METHODS: According to the time varying elastance concept, MVo2 is determined by contractility (Emax) and total mechanical work (PLA), which is the sum of the external work (EW) and potential energy (PE). Mechanical efficiency (EW/MVo2) equals the product of EW/PLA (= efficiency of energy transfer or EET) and PLA/MVo2. Emax is the slope of the end systolic pressure-segment length relationship, determined by gradually clamping the aorta. PLA is the area enclosed by the end systolic pressure-segment length relationship and the pressure-segment length trajectory. EW is the area of the pressure-segment length loop. Systemic haemodynamics, regional segment shortening, and MVo2 were determined at baseline, during stunning (two sequences of 10 min occlusion and 30 min of reperfusion), after a subsequent 50 beats·min-1 increase in heart rate by atrial pacing and additional infusion of 2 μg·kg-1·min-1 dobutamine.RESULTS: Stunning decreased segment shortening from 18.2(SEM 1.9)% to 10.2(1.5)%, MVo2 from 4.16(0.27) x 10-2 to 2.84(0.25) x 10-2 μmol·beat-1·g-1, and Emax from 47(9) to 23(3) mm Hg·mm-1 (all p&lt;0.05). PLA decreased by 13(4)%, as EW decreased by 42(6)%, and PE tended to increase. Although EET decreased from 0.58(0.04) to 0.40(0.03) (p&lt;0.05), there was no decrease in the mechanical efficiency, as an increase in PE caused an increase in PLA/MVo2 which compensated for the decrease in EET. Dobutamine infusion increased Emax and EW per beat to 120(23)% and 67(8)% of baseline, respectively, while MVo2 [4.12(0.53) μmol·beat-1·g-1] and EET [0.57(0.04)] returned to baseline.CONCLUSIONS: In stunned myocardium, mechanical efficiency is not decreased despite a decrease in EET. The increase in EET after dobutamine may explain the lack of the excessive increase in MVo2.</p