Emerging trends in mediastinitis: National Veterans Health Administration experience with methicillin-resistant Staphylococcus aureus prevention.

OBJECTIVES: Perioperative bacterial decolonization and prophylactic antibiotic therapy at the Veterans Affairs Health Care System have changed over the past decade. Our objectives were to identify associated changes in the microbiology of mediastinitis and to perform a contemporary survival analysis in patients with mediastinitis after isolated coronary artery bypass grafting procedure. METHODS: From January 2006 to December 2015, 45,323 consecutive patients underwent coronary artery bypass grafting at 83 medical centers. The Veterans Affairs Health Care System nationwide administrative database was queried to identify patients with postoperative mediastinitis and obtain patient-level data. Simple descriptive statistics and multivariable logistic regression were used to analyze microbiologic data and identify risk factors for infection. Poisson regression was used to determine yearly incidence estimates. Cox proportional hazard model identified predictors of long-term survival from date of operation. RESULTS: During the study period, 348 patients (0.78%) developed postoperative mediastinitis-with a stable rate of incidence (Cochrane-Armitage test, P = .69). Of patients with microbiologic data, 75.5% of infections (n = 188) were caused by gram-positive and 24.5% (n = 61) gram-negative organisms. The incidence of methicillin-resistant Staphylococcus aureus mediastinitis decreased during the study period (Cochrane-Armitage test, P = .013). Gram-negative mediastinitis occurred earlier than gram-positive mediastinitis (median, 15.0 vs 25.0 days; P < .0001). Patients with mediastinitis did not have increased 30-day mortality (2.0% vs 1.9%; P = .9), but had worse long-term survival compared with uninfected patients (P < .0001). CONCLUSIONS: The incidence of methicillin-resistant S aureus mediastinitis has decreased over the past decade. Gram-negative bacteria are responsible for 1 in 4 cases of mediastinitis and infection is diagnosed earlier in the postoperative period than gram-positive mediastinitis. These findings highlight the need for efforts to prevent gram-negative and methicillin-susceptible S aureus mediastinitis.

Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.

BACKGROUND: Energy conservation and calcium homeostasis contribute to myocardial protection provided by hyperkalemic cardioplegia during ischemia. Complimenting these established mechanisms of protection, previous work suggested that activation of cytoprotective signaling pathways also contributes to reduced injury with cardioplegia. We proposed that cardioplegia would recruit cytoprotective pathways and investigated the transcriptional response of the heart after cardioplegia-protected ischemia compared with that after ischemia alone. METHODS: Isolated perfused rat hearts underwent 40 minutes of global ischemia alone or with St Thomas cardioplegia, followed by 120 minutes of reperfusion. The expression profiles of isolated RNA were determined by using Affymetrix microarrays and assessed by comparing cardioplegia-protected hearts and hearts undergoing unprotected ischemia with time-matched control hearts. The content of selected proteins was assessed by means of immunoblotting. RESULTS: Cardioplegia preserved the expression of multiple genes involved in carbohydrate and fatty acid metabolism, glycolysis, and electron transport compared with ischemia alone. The expression of the sodium-calcium exchanger and ryanodine receptor was preserved in line with the ability of cardioplegia to decrease calcium overload. The expression of multiple cytoprotective molecules, including protein-tyrosine kinase, calcineurin B, p38 mitogen-activated protein kinase, voltage-dependent anion channel, protein kinase C , heat shock protein 70, and manganese superoxide dismutase all showed decreased expression in ischemia but were preserved to near nonischemic levels by cardioplegia. CONCLUSION: Cardioplegia during ischemia maintained an expression profile similar to that seen in nonischemic hearts for genes involved in energy conservation, calcium homeostasis, and cytoprotective pathways, whereas ischemia alone did not. Exposing the transcriptional differences in cytoprotective genes during untreated and cardioplegia-treated ischemia provides valuable insight into an additional mechanism of cardioprotection induced by cardioplegia.

Cardioprotection by St Thomas' solution is mediated by protein kinase C and tyrosine kinase.

BACKGROUND: Intracellular signaling pathways, specifically the activation of protein kinase C and tyrosine kinase, are essential to the cardioprotection of ischemic preconditioning. We proposed that activation of PKC and TK contribute to the myocardial protection of St. Thomas' No. 2 cardioplegia solution (STC). MATERIALS AND METHODS: Isolated rat hearts were exposed to 40 min of global ischemia followed by 120 min of reperfusion. Before ischemia, hearts received no treatment (control; n = 7), STC (n = 7), phorbol 12-myristate 13-acetate (PMA; n = 6), PMA + chelerythrine (n = 6), anisomycin (n = 6), anisomycin + genistein (n = 7), STC + chelerythrine (n = 7), STC + genistein (n = 7), PMA + genistein (n = 7) or anisomycin + chelerythrine (n = 7). Left ventricular developed pressure (LVDP) recovery, myocardial infarct size, and lactate dehydrogenase release were measured. RESULTS: STC as well as PMA (protein kinase C activator) and anisomycin (tyrosine kinase activator) significantly reduced infarct size (6.9 +/- 2.9%, 9.6 +/- 2.1%, 14.0 +/- 4.4%) compared with controls (42.4 +/- 2.9%, P < 0.05). The infarct reduction of PMA and anisomycin were blocked by their inhibitors chelerythrine and genistein, respectively. Both chelerythrine (29.2 +/- 4.1%, P < 0.05) and genistein (40.4 +/- 4.3%, P < 0.05) attenuated the reduction of infarct size provided by STC. The recovery of LVDP improved with STC, PMA and anisomycin (72.6 +/- 1.4%, 60.4 +/- 4.7%, 57.2 +/- 4.6%) compared with control (33.8 +/- 3.6%, P < 0.05). Addition of chelerythrine or genistein to STC impaired recovery of LVDP (52.3 +/- 4.4%, 35.1 +/- 2.5%, P < 0.05) compared with STC treatment. CONCLUSION: Administration of the pharmacologic inhibitors chelerythrine and genistein blunts the cardioprotection caused by STC treatment.

Aortomyoplasty: hemodynamics and comparison to the intraaortic balloon pump.

BACKGROUND: Aortomyoplasty (AMP), a procedure in which the latissimus dorsi muscle (LDM) is wrapped around the aorta and stimulated during diastole, is a potential method of chronic counterpulsation. Counterpulsation by the intraaortic balloon pump (IABP) is a proven treatment for ischemic coronary syndrome and heart failure but cannot be used chronically. This study examined the long-term potential of a unique AMP configuration and compared its performance to the IABP. MATERIALS AND METHODS: AMP was done using a wringer configuration (AMP-W) in nine dogs. Six and 12 months later, acute hemodynamic augmentation was evaluated by measuring differences in mean diastolic aortic pressure (mDAP), peak left ventricular pressure (pLVP), and the endocardial viability ratio (EVR) between stimulated and unstimulated beats. RESULTS: The diastolic augmentation obtained by AMP-W at 6 months and by AMP-W and IABP at 12 months was statistically significant. Additionally, the enhancements in EVR (16.1 +/- 4.3%), mDAP (8.6 +/- 2.5%), and pLVP (-1.8 +/- 1.0%) at 6 months were similar to those in EVR (19.1 +/- 5.2%), mDAP (13.1 +/- 3.6%), and pLVP (-0.8 +/- 1.3%) at 12 months. Most importantly, the augmentation obtained by AMP-W at 12 months was similar to that of the IABP: EVR (17.1 +/- 5.9%), mDAP (13.4 +/- 6.7%), and pLVP (-1.5 +/- 0.8%). CONCLUSIONS: AMP-W is a safe, robust procedure, capable of providing counterpulsation equivalent to the IABP, 12 months following surgery. The potential for AMP-W to offer chronic counterpulsation and to benefit the ischemic heart should be investigated further.

Circulatory benefits of diastolic counterpulsation in an ischemic heart failure model after aortomyoplasty.

OBJECTIVE: Aortomyoplasty is an experimental surgical procedure in which the latissimus dorsi muscle is wrapped around the thoracic aorta and stimulated to contract during diastole, providing diastolic counterpulsation. We hypothesized that aortomyoplasty could improve cardiac function in a chronic ischemic heart failure model, similar to the improvement seen with the intra-aortic balloon pump. METHODS: Six dogs (25-30 kg) successfully underwent aortomyoplasty followed by serial coronary microembolization. Ejection fraction decreased from 63.5% to 36.5%. Two weeks after the final microembolization, the muscle was conditioned for 4 months to achieve fatigue resistance. One year after aortomyoplasty, hemodynamic studies during 1 hour of aortomyoplasty and 1 hour of intra-aortic balloon counterpulsation determined mean diastolic aortic pressure, peak left ventricular pressure, and endocardial viability ratio for assisted and unassisted beats. Cardiac output, stroke volume, and parameters of cardiac function were also measured. RESULTS: Endocardial viability ratio increased by 23.8% +/- 7.9% (P =.001) with aortomyoplasty counterpulsation and by 22.7% +/- 12.9% (P =.021) with the intra-aortic balloon pump. Both aortomyoplasty and the intra-aortic balloon pump significantly increased mean diastolic aortic pressure and reduced peak left ventricular pressure. Improvements in cardiac function with aortomyoplasty and the intra-aortic balloon pump were similar. Cardiac output increased from 2.61 +/- 0.88 to 3.07 +/- 1.06 L/min (P =.006), and index of afterload decreased from 5.4 +/- 1.4 to 4.8 +/- 1.4 mm Hg/mL (P =.02) during 1 hour of aortomyoplasty counterpulsation. CONCLUSION: One year after the procedure, aortomyoplasty counterpulsation provided diastolic augmentation and improved cardiac performance similar to the improvement provided by the intra-aortic balloon pump in a chronic ischemic heart failure model. Aortomyoplasty has the potential to benefit patients with ischemic heart disease refractory to current therapies.

Reducing Mortality Among Elderly Patients Undergoing Urgent Surgical Revascularization for Acute Myocardial Infarction.

INTRODUCTION: Elderly patients undergoing coronary bypass surgery after acute myocardial infarction represent a distinct, high risk subgroup. We sought to identify independent risk factors for mortality in a series of patients operated on in our hospital. METHODS: The case records of 499 consecutive patients greater than 70 years were identified, and 94 of these patients underwent urgent/emergent coronary bypass surgery within 7 days of acute myocardial infarction. Patients received either cold (4°C) or tepid (32°C) cardioplegia for myocardial protection. RESULTS: Mortality for the tepid cardioplegia group was 0/33, and the mortality for the cold cardioplegia group was 12/61 (0% vs. 20%, p equals 0.003). Multivariate analysis demonstrated left ventricular dysfunction and cold blood cardioplegia to be independent predictors of mortality. CONCLUSION: The type of myocardial protection technique is a significant predictor of mortality, and tepid cardioplegia may provide significant advantages to this high risk patient population.