Loss of Independent Living in Patients Undergoing Transcatheter or Surgical Aortic Valve Replacement: A Retrospective Cohort Study.

BACKGROUND: The recommendation for transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in patients 65 to 80 years of age is equivocal, leaving patients with a difficult decision. We evaluated whether TAVR compared to SAVR is associated with reduced odds for loss of independent living in patients ≤65, 66 to 79, and ≥80 years of age. Further, we explored mechanisms of the association of TAVR and adverse discharge. METHODS: Adult patients undergoing TAVR or SAVR within a large academic medical system who lived independently before the procedure were included. A multivariable logistic regression model, adjusting for a priori defined confounders including patient demographics, preoperative comorbidities, and a risk score for adverse discharge after cardiac surgery, was used to assess the primary association. We tested the interaction of patient age with the association between aortic valve replacement (AVR) procedure and loss of independent living. We further assessed whether the primary association was mediated (ie, percentage of the association that can be attributed to the mediator) by the procedural duration as prespecified mediator. RESULTS: A total of 1751 patients (age median [quartiles; min-max], 76 [67, 84; 23-100]; sex, 56% female) were included. A total of 27% (222/812) of these patients undergoing SAVR and 20% (188/939) undergoing TAVR lost the ability to live independently. In our cohort, TAVR was associated with reduced odds for loss of independent living compared to SAVR (adjusted odds ratio [OR adj ] 0.19 [95% confidence interval {CI}, 0.14-0.26]; P < .001). This association was attenuated in patients ≤65 years of age (OR adj 0.63 [0.26-1.56]; P = .32) and between 66 and 79 years of age (OR adj 0.23 [0.15-0.35]; P < .001), and magnified in patients ≥80 years of age (OR adj 0.16 [0.10-0.25]; P < .001; P -for-interaction = .004). Among those >65 years of age, a shorter procedural duration mediated 50% (95% CI, 28-76; P < .001) of the beneficial association of TAVR and independent living. CONCLUSIONS: Patients >65 years of age undergoing TAVR compared to SAVR had reduced odds for loss of independent living. This association was partly mediated by shorter procedural duration. No association between AVR approach and the primary end point was found in patients ≤65 years of age.

Geometric Indices for Predicting Ischemic Mitral Regurgitation: Correlation of Mitral Valve Coaptation Area With Tenting Height, Tenting Area and Tenting Volume.

OBJECTIVES: Ischemic remodeling of the left ventricle in patients with coronary artery disease (CAD) results in geometric changes of the mitral valve (MV) apparatus, leading to reduced MV leaflet coaptation. Although the calculation of the coaptation area has value in assessing the effects of left ventricular remodeling on the MV, it is difficult and time-consuming to measure. In this study the authors hypothesized that the tenting volume (TV) would have a greater association with coaptation area than tenting height (TH) or tenting area (TA). DESIGN: A retrospective review. SETTING: A single tertiary-care academic hospital. PARTICIPANTS: There were 145 adult patients who underwent coronary artery bypass graft surgery between April 2018 and July 2020. MEASUREMENTS AND MAIN RESULTS: Intraoperative 2- and 3-dimensional transesophageal echocardiographic studies were obtained in the precardiopulmonary bypass period. Offline analysis was used to obtain TH, TA, TV and coaptation area for each patient. Correlation between the coaptation area and the TH, TA, and TV was conducted using Pearson's correlation. The median age of the population was 68.0 years (61.0-73.3), the body mass index was 29.0 kg/m2 (25.7-33.5), and 17.8% were females. Increases in TV were the most reliable predictor of decreases in coaptation area (R2 = 0.75) followed by TA (R2 = 0.48) and TH (R2 = 0.47). CONCLUSION: As a representative of the complete topography of the MV, the authors' study demonstrated that in patients with CAD, TV has a greater negative correlation with coaptation area as compared to TH or TA.

Timing of Blood Transfusions and 30-Day Patient Outcomes After Coronary Artery Bypass Graft Surgery.

OBJECTIVE: Packed red blood cell transfusion during coronary artery bypass graft surgery is known to be associated with adverse outcomes. However, the association of the timing between transfusions in relation to discharge and 30-day postoperative outcomes has not been studied. The study authors investigated the impact of transfusion timing on 30-day surgical outcomes. DESIGN: A retrospective review. SETTING: At a single tertiary-care academic hospital. PARTICIPANTS: A total of 2,481 adult patients underwent primary coronary artery bypass graft surgery between January 2014 and December 2020. MEASUREMENTS AND MAIN RESULTS: The relationship between the timing of packed red blood cell transfusion (intraoperative, postoperative, or both) and 30-day postoperative outcome variables was calculated as an odds ratio. The influence of timing of transfusion on adjusted probability of postoperative complications was plotted against the lowest intraoperative hematocrit. The median age of the population was 67 years (60.0-74.0), body mass index was 28.5 (25.6-32.3) kg/m2, and 497 (20.0%) were female. A total of 1,588 (36%) patients received packed red blood cell transfusions; 182 (7.3%) received intraoperative transfusions, 489 (19.7%) received postoperative transfusions, and 222 (9.0%) received both (intraoperative and postoperative transfusions). Postoperative transfusion was associated with significantly higher odds of readmission (1.83 [1.32-2.54], p = 0.002) and heart failure (1.64 [1.2-2.23], p = 0.008) compared to patients with no transfusions; whereas intraoperative transfusions were not. CONCLUSION: The authors' data suggested that the postoperative timing of transfusion in patients undergoing coronary artery bypass graft surgery may be associated with an increased incidence of 30-day heart failure and readmission. Prospective research is needed to conclusively confirm these findings.

Intraoperative Oxygen Practices in Cardiac Surgery: A National Survey.

OBJECTIVE: To describe the current nationwide perspectives and practice regarding intraoperative oxygen titration in cardiac surgery. DESIGN: Prospective, observational survey. SETTING: Hospitals across the United States. PARTICIPANTS: Cardiovascular anesthesiologists and perfusionists. INTERVENTIONS: Expert- and consensus-derived electronic surveys were sent to perfusionists and cardiac anesthesiologists to evaluate the current intraoperative practices around oxygen administration. Providers were asked about individual intraoperative oxygen titration practices used at different stages of cardiac surgical procedures. Anonymous responses were collected in the Research Electronic Data Capture (REDCap). MEASUREMENTS AND MAIN RESULTS: A total of 3,335 providers were invited to participate, of whom 554 (317 anesthesiologists and 237 perfusionists) were included in the final analysis (17% response rate). During cardiopulmonary bypass (CPB), perfusionists reported a median (interquartile range [IQR]) target range from 150 (110-220)-to-325 mmHg (250-400), while anesthesiologists reported a significantly lower target range from 90 (70-150)-to-250 mmHg (158-400) (p values <0.0001 and 0.02, respectively). This difference was most pronounced at lower partial pressure of arterial oxygen (PaO2) ranges. The median PaO2 considered "too low" by perfusionists was 100 mmHg (IQR 80-125), whereas it was 60 mmHg (IQR 60-75) for anesthesiologists, who reported for both off and on bypass. The median PaO2 considered "too high" was 375 mmHg (IQR 300-400) for perfusionists and 300 mmHg (IQR 200-400) for anesthesiologists. Anesthesiologists, therefore, reported more comfort with significantly lower PaO2 values (p < 0.0001), and considered a higher PaO2 value less desirable compared with perfusionists (p < 0.0001). CONCLUSIONS: This survey demonstrated there was wide variation in oxygen administration practices between perfusionists and anesthesiologists. Hyperoxygenation was more common while on CPB.

An Algorithmic Approach to the Surgical Management of Sternal Dehiscence: A Single-Center Experience.

BACKGROUND: Deep sternal wound complications following sternotomy represent a complex challenge. Management can involve debridement, flap reconstruction, and rigid sternal fixation (RSF). We present our 11-year experience in the surgical treatment of deep sternal wound dehiscence using a standardized treatment algorithm. METHODS: A retrospective review was conducted of all 134 cardiac patients who required operative debridement after median sternotomy at a single institution between October 2007 and March 2019. Demographics, perioperative covariates, and outcomes were recorded. Univariate and subgroup analyses were performed. RESULTS: One-hundred twelve patients (83.5%) with a deep sternal dehiscence underwent flap closure and 56 (50%) RSF. Of the patients who underwent flap closure, 87.5% received pectoralis advancement flaps. A 30-day mortality following reconstruction was 3.9%. Median length of stay after initial debridement was 8 days (interquartile range: 5-15). Of patients with flaps, 54 (48%) required multiple debridements prior to closure, and 30 (27%) underwent reoperation after flap closure. Patients who needed only a single debridement were significantly less likely to have a complication requiring reoperation (N = 10/58 vs. 20/54, 17 vs. 37%, p = 0.02), undergo a second flap (N = 6/58 vs. 17/54, 10 vs. 32%, p < 0.001), or, if plated, require removal of sternal plates (N = 6/34 vs. 11/22, 18 vs. 50%, p = 0.02). CONCLUSION: Although sternal dehiscence remains a complex challenge, an aggressive treatment algorithm, including debridement, flap closure, and consideration of RSF, can achieve good long-term outcomes. In low-risk patients, RSF does not appear to increase the likelihood of reoperation. We hypothesize that earlier surgical intervention, before the development of systemic symptoms, may be associated with improved outcomes.

Intraoperative Oxygen Concentration and Neurocognition after Cardiac Surgery.

BACKGROUND: Despite evidence suggesting detrimental effects of perioperative hyperoxia, hyperoxygenation remains commonplace in cardiac surgery. Hyperoxygenation may increase oxidative damage and neuronal injury leading to potential differences in postoperative neurocognition. Therefore, this study tested the primary hypothesis that intraoperative normoxia, as compared to hyperoxia, reduces postoperative cognitive dysfunction in older patients having cardiac surgery. METHODS: A randomized double-blind trial was conducted in patients aged 65 yr or older having coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 100 patients were randomized to one of two intraoperative oxygen delivery strategies. Normoxic patients (n = 50) received a minimum fraction of inspired oxygen of 0.35 to maintain a Pao2 above 70 mmHg before and after cardiopulmonary bypass and between 100 and 150 mmHg during cardiopulmonary bypass. Hyperoxic patients (n = 50) received a fraction of inspired oxygen of 1.0 throughout surgery, irrespective of Pao2 levels. The primary outcome was neurocognitive function measured on postoperative day 2 using the Telephonic Montreal Cognitive Assessment. Secondary outcomes included neurocognitive function at 1, 3, and 6 months, as well as postoperative delirium, mortality, and durations of mechanical ventilation, intensive care unit stay, and hospital stay. RESULTS: The median age was 71 yr (interquartile range, 68 to 75), and the median baseline neurocognitive score was 17 (16 to 19). The median intraoperative Pao2 was 309 (285 to 352) mmHg in the hyperoxia group and 153 (133 to 168) mmHg in the normoxia group (P < 0.001). The median Telephonic Montreal Cognitive Assessment score on postoperative day 2 was 18 (16 to 20) in the hyperoxia group and 18 (14 to 20) in the normoxia group (P = 0.42). Neurocognitive function at 1, 3, and 6 months, as well as secondary outcomes, were not statistically different between groups. CONCLUSIONS: In this randomized controlled trial, intraoperative normoxia did not reduce postoperative cognitive dysfunction when compared to intraoperative hyperoxia in older patients having cardiac surgery. Although the optimal intraoperative oxygenation strategy remains uncertain, the results indicate that intraoperative hyperoxia does not worsen postoperative cognition after cardiac surgery.

Atorvastatin regulates apoptosis in chronically ischemic myocardium.

BACKGROUND: We previously demonstrated that atorvastatin upregulates proangiogenic proteins and increases arteriolar density in ischemic myocardium. Despite this, there was a lack of collateral-dependent perfusion, possibly related to apoptosis. We utilized a swine model of metabolic syndrome and chronic myocardial ischemia to investigate the effects of atorvastatin on apoptosis. MATERIALS AND METHODS: Sixteen Ossabaw miniswine were fed a high-cholesterol diet for 14 weeks then underwent surgical placement of an ameroid constrictor to their circumflex artery inducing chronic ischemia. Eight pigs additionally received supplemental atorvastatin (1.5 mg/kg daily). Myocardium was harvested six months later for western blotting and TUNEL staining. RESULTS: Animals supplemented with atorvastatin had significant increases in markers associated with apoptosis including p-38, BAX, and caspase 3 (p < 0.05). Atorvastatin supplementation also resulted in significant increases in expression of cell survival proteins Bcl-2 and P-ERK and an overall decrease in apoptosis demonstrated by TUNEL staining (p < 0.05). CONCLUSIONS: Atorvastatin acts on multiple pathways and its effects on angiogenesis remain unclear. Although there is increased expression in several markers of apoptosis, key anti-apoptotic proteins were also upregulated with an overall decrease in apoptosis. Further investigation of these pathways may provide insight into the role of statins on myocardial protection after ischemia.

Altered apoptosis-related signaling after cardioplegic arrest in patients with uncontrolled type 2 diabetes mellitus.

BACKGROUND: We investigated the effects of cardioplegic arrest and reperfusion (CP/Rep) on myocardial apoptosis and key apoptotic mediators, such as apoptosis-inducing factor, caspase 3, caspase 8, caspase 9, poly(adenosine diphosphate-ribose) polymerase, B-cell lymphoma 2 (Bcl-2) family proteins, and protein kinase C (PKC), in uncontrolled type 2 diabetic, controlled type 2 diabetic, and nondiabetic patients. METHODS AND RESULTS: Right atrial tissue was harvested pre- and post-CP/Rep from uncontrolled type 2 diabetic patients (hemoglobin A1c=9.6 ± 0.25), controlled type 2 diabetic patients (hemoglobin A1c=6.5 ± 0.15), and nondiabetic patients (hemoglobin A1c=5.4 ± 0.12) undergoing coronary artery bypass grafting (n=8/group). Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was used for the identification of apoptotic cells. Total and modified apoptosis-inducing factor, Bcl-2 family proteins, phospho-PKC-α, phospho-PKC-ß1, and poly(adenosine diphosphate-ribose) polymerase were quantified by immunoblotting or immunohistochemistry. At baseline, the number of apoptotic cells and expression of total apoptosis-inducing factor, Bcl-2, Bak, and Bax in the pre-CP/Rep atrial tissue from uncontrolled type 2 diabetic patients were significantly increased compared with those of nondiabetic or controlled type 2 diabetic patients (P<0.05). After CP/Rep, the amount of apoptotic cells, apoptosis-inducing factor, phospho-Bad, phospho-PKC-α, phospho-PKC-ß1, and cleaved poly(adenosine diphosphate-ribose) polymerase in post-CP/Rep atrial tissue were increased in all 3 groups compared with pre-CP/Rep. These increases after CP/Rep were more pronounced in the uncontrolled type 2 diabetic group. In addition, there were significant increases in the expression of cleaved caspase 8 and caspase 9 in the basal and post-CP/Rep atrium of uncontrolled type 2 diabetic group compared with nondiabetic or controlled type 2 diabetic group. CONCLUSIONS: Uncontrolled diabetes mellitus is associated with increases in myocardial apoptosis and expression of key apoptosis mediators at baseline and in the setting of CP/Rep.

Metformin mitigates apoptosis in ischemic myocardium.

BACKGROUND: Epidemiologic data has shown that metformin confers a survival advantage in patients with cardiovascular disease. Although the underlying cardioprotective mechanism is unclear, it appears to be independent of metformin's insulin-sensitizing effect. The purpose of this study was to evaluate the effect of metformin on the apoptosis pathway in the ischemic and nonischemic cardiac tissue in a swine model of metabolic syndrome. MATERIALS AND METHODS: Ossabaw miniswine were fed either a regular diet (Ossabaw control, n = 8), a high-cholesterol diet (Ossabaw high cholesterol, n = 8), or a high-cholesterol diet supplemented with metformin (Ossabaw high-cholesterol metformin, n = 8). After 9 wk, all animals underwent placement of an ameroid constrictor to the left circumflex coronary artery to induce chronic ischemia. Seven weeks after ameroid placement, animals underwent cardiac harvest. RESULTS: In the chronically ischemic myocardium, metformin significantly upregulates prosurvival proteins: extracellular signal-regulated kinases, nuclear factor κB, phosphorylated endothelial nitric oxide synthase, and P38. Metformin also significantly inhibits or downregulates proapoptosis proteins: FOXO3 and caspase 3. Metformin decreased the percent apoptotic cells in the ischemic and nonischemic myocardium. There was no difference in arteriolar density, capillary density, intramyocardial fibrosis, or collagen deposition in the ischemic or nonischemic myocardium. CONCLUSIONS: Metformin selectively alters the apoptosis pathway by inhibiting FOXO3 and decreasing the active form of caspase 3, cleaved caspase 3. Metformin also upregulates mitogen-activated kinase proteins p38 and extracellular signal-regulated protein kinases 1 and 2, which are considered cardioprotective during ischemic preconditioning. Perhaps, the altered activation of the apoptosis pathway in ischemic myocardium is one mechanism by which metformin is cardioprotective.

Microvascular notch signaling is upregulated in response to vascular endothelial growth factor and chronic myocardial ischemia.

BACKGROUND: Notch signaling is a highly conserved pathway that promotes vascular and myocardial growth. The hypothesis that exogenous vascular endothelial growth factor (VEGF) administration to ischemic myocardium would enhance the neovascular response and upregulate Notch signaling was assessed. METHODS AND RESULTS: Fourteen male Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex artery to induce chronic myocardial ischemia with half of the animals receiving perivascular VEGF to the ischemic area. The remote territory served as the normal ventricle control (NV), while the 2 experimental groups consisted of the area at risk of the non-VEGF animals (AAR) and the area at risk of animals treated with VEGF (VEGF). Capillary and arteriolar density was significantly increased in the VEGF group as compared to both NV and AAR. Expression of Notch receptors and pro-neovascular Notch ligands was significantly higher in the VEGF group. Both Jagged 1 and Notch 3 were the most highly concentrated in the smooth muscle wall of arterioles. CONCLUSIONS: VEGF administration to chronically ischemic myocardium significantly augmented the neovascular response by an increase in both capillary and arteriolar density, and resulted in an upregulation of several Notch receptors and ligands, which were not upregulated with ischemia alone. These findings suggest that the augmented neovascular response seen with VEGF administration was through the VEGF-induced upregulation of Notch signaling.

Sternal bone anatomy on preoperative imaging as an independent predictor of deep sternal dehiscence following median sternotomy.

Complications following median sternotomy are associated with morbidity, mortality, and major healthcare costs. With plastic surgeons being increasingly consulted to close complex sternotomy wounds, a more accurate risk stratification tool for this comorbid patient population is warranted. This study examines the association of preoperative radiologic sternal measurements and deep sternal dehiscence, comparing this with other known clinical risk factors. A decreased manubrium sternal thickness relative to body weight (<0.13 mm/kg) and an absolute inferior sternal width ≤13.8 mm had a significant association with the development of deep sternal dehiscence, even with adjustment for known clinical risk factors. With such measurements assisting in further risk stratification, the opportunity to improve risk assessment holds value for plastic and reconstructive surgeons who are consulted to close extensive sternotomy wounds.

Changes in microvascular reactivity after cardiopulmonary bypass in patients with poorly controlled versus controlled diabetes.

BACKGROUND: We investigated the effects of cardiopulmonary bypass (CPB) on peripheral arteriolar reactivity and associated signaling pathways in poorly controlled (UDM), controlled (CDM), and case-matched nondiabetic (ND) patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS: Skeletal muscle arterioles were harvested before and after CPB from the UDM patients (hemoglobin A1c [HbA1c]=9.0 ± 0.3), the CDM patients (HbA1c=6.3 ± 0.15), and the ND patients (HbA1c=5.2 ± 0.1) undergoing CABG surgery (n=10/group). In vitro relaxation responses of precontracted arterioles to endothelium-dependent vasodilators adenosine 5'-diphosphate (ADP) and substance P and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined. The baseline responses to ADP, substance P, and SNP of arterioles from the UDM patients were decreased as compared with microvessels from the ND or CDM patients (P<0.05). The post-CPB relaxation responses to ADP and substance P were significantly decreased in all 3 groups compared with pre-CPB responses (P<0.05). However, these decreases were more pronounced in the UDM group (P<0.05). The post-CPB response to SNP was significantly decreased only in the UDM group, not in the other 2 groups compared with pre-CPB. The expression of protein kinase C (PKC)-α, PKC-ß, protein oxidation, and nitrotyrosine in the skeletal muscle were significantly increased in the UDM group as compared with those of ND or CDM groups (P<0.05). CONCLUSIONS: Poorly controlled diabetes results in impaired arteriolar function before and after CPB. These alterations are associated with the increased expression/activation of PKC-α and PKC-ß and enhanced oxidative and nitrosative stress.

Effects of red wine and vodka on collateral-dependent perfusion and cardiovascular function in hypercholesterolemic swine.

BACKGROUND: Moderate consumption of alcohol, particularly red wine, has been shown to decrease cardiac risk. We used a hypercholesterolemic swine model of chronic ischemia to examine the effects of 2 alcoholic beverages on the heart. METHODS AND RESULTS: Yorkshire swine fed a high-cholesterol diet underwent left circumflex ameroid constrictor placement to induce chronic ischemia at 8 weeks of age. One group (HCC, n=9) continued on the diet alone, the second (HCW, n=8) was supplemented with red wine (pinot noir, 12.5% alcohol, 375 mL daily), and the third (HCV, n=9) was supplemented with vodka (40% alcohol, 112 mL daily). After 7 weeks, cardiac function was measured, and ischemic myocardium was harvested for analysis of perfusion, myocardial fibrosis, vessel function, protein expression, oxidative stress, and capillary density. Platelet function was measured by aggregometry. Perfusion to the ischemic territory as measured by microsphere injection was significantly increased in both HCW and HCV compared with HCC at rest, but in only the HCW group under ventricular pacing. Microvessel relaxation response to adenosine 5'-diphosphate was improved in the HCW group alone as was regional contractility in the ischemic territory, although myocardial fibrosis was decreased in both HCW and HCV. Expression of proangiogenic proteins phospho-endothelial nitric oxide synthase and vascular endothelial growth factor was increased in both HCW and HCV, whereas phospho-mammalian target of rapamycin was increased only in the HCV group. Expression of Sirt-1 and downstream antioxidant phospho-FoxO1 was increased only in the HCW group. Protein oxidative stress was decreased in the HCW group alone, whereas capillary density was increased only in the HCV group. There was no significant difference in platelet function between groups. CONCLUSION: Moderate consumption of red wine and vodka may reduce cardiovascular risk by improving collateral-dependent perfusion through different mechanisms. Red wine may offer increased cardioprotection related to its antioxidant properties.

Novel use of interosseous absorbable mattress sutures for secondary sternal fixation: A case series.

There is currently no consensus on the treatment of median sternotomy patients presenting secondarily with deep sternal wound infection or symptomatic sternal nonunion. We have developed a novel approach to sternal bone fixation when concerns for open wounds or microbial colonization preclude the use of permanent hardware placement: (1) sternal closure with absorbable interosseous monocortical horizontal mattress sutures followed by (2) multilayered soft tissue closure with pectoralis major advancement or turnover flaps. Benefits of this technique include: closure of retrosternal dead-space, tension offloading of the soft tissue closure, repair of transverse sternal fractures, and preservation of internal mammary artery (IMA) perforators for potential pectoralis turnover flaps. In our early experience, this technique has been successful at promoting functional sternal union - even in secondary closure of high-risk patients contraindicated for permanent hardware placement.

Neuropeptide Y improves myocardial perfusion and function in a swine model of hypercholesterolemia and chronic myocardial ischemia.

Pharmacologically induced angiogenesis could be a promising option in clinical situations with diffuse inoperable coronary artery disease e.g. metabolic syndrome and diabetes mellitus. The failure of focused cytokine, stem cell and gene therapies to achieve both perfusion and functional improvement in clinical trials suggests a more centralized control mechanism. Neuropeptide-Y (NPY) is one such natural neurotransmitter that is known to exert a multifaceted role during neo-angiogenesis and can possibly act as the central control. To date, the ability to harness the 'master switch' nature of NPY in a specific experimental model of metabolic syndrome and chronic myocardial ischemia has not been conclusively demonstrated. We hypothesized that infiltration of NPY into an area of chronic ischemia in a metabolic syndrome swine model would induce angiogenesis and improve myocardial perfusion and function. An osmotic pump was inserted three weeks after surgical induction of focal myocardial ischemia. We delivered either NPY or placebo for five weeks, after which the myocardial tissue was harvested for analysis. Assessments of myocardial perfusion and function were performed at each stage of the experiment. Local infiltration of NPY significantly improved collateral vessel formation, blood flow and myocardial function. We believe activation of NPY receptors may be a potential target therapy for patients with diffuse coronary artery disease.

Effects of cyclooxygenase inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia.

The cardiovascular effects of cyclooxygenase (COX) inhibition remain controversial, especially in the setting of cardiovascular comorbidities. We examined the effects of nonselective and selective COX inhibition on cardiovascular function in a hypercholesterolemic swine model of chronic ischemia. Twenty-four intact male Yorkshire swine underwent left circumflex ameroid constrictor placement and were subsequently given either no drug (HCC; n = 8), a nonselective COX inhibitor (440 mg/day naproxen; HCNS; n = 8), or a selective COX-2 inhibitor (200 mg/day celecoxib; HCCX; n = 8). After 7 wk, myocardial functional was measured and myocardium from the nonischemic ventricle and ischemic area-at-risk (AAR) were analyzed. Regional function as measured by segmental shortening was improved in the AAR of HCCX compared with HCC. There was no significant difference in perfusion to the nonischemic ventricle between groups, but myocardial perfusion in the AAR was significantly improved in the HCCX group compared with controls at rest and during pacing. Endothelium-dependent microvessel relaxation was diminished by ischemia in HCC animals, but both naproxen and celecoxib improved vessel relaxation in the AAR compared with controls, and also decreased the vasoconstrictive response to serotonin. Thromboxane levels in the AAR were decreased in both HCNS and HCCX compared with HCC, whereas prostacyclin levels were decreased only in HCNS, corresponding to a decrease in prostacyclin synthase expression. Chronic ischemia increased apoptosis in Troponin T negative cells and intramyocardial fibrosis, both of which were reduced by celecoxib administration in the AAR. Capillary density was decreased in both the HCNS and HCCX groups. Protein oxidative stress was decreased in both HCNS and HCCX, whereas lipid oxidative stress was decreased only in the HCCX group. Thus nonselective and especially selective COX inhibition may have beneficial myocardial effects in the setting of hypercholesterolemia and chronic ischemia. Whether these effects modulate cardiovascular risk in patients taking these drugs remains to be seen, but evidence to date suggests that they do not.

Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia.

Ossabaw miniswine have been naturally selected to efficiently store large amounts of lipids offering them a survival advantage. Our goal was to evaluate the myocardial response to chronic ischemia of the Ossabaw consuming a hypercaloric, high-fat/cholesterol diet with and without metformin supplementation. At 6 weeks of age animals were fed either a regular diet (OC, n = 9), a hypercaloric high-fat/cholesterol diet (OHC, n = 9), or a hypercaloric high-fat/cholesterol diet supplemented with metformin (OHCM, n = 8). At 9 weeks, all animals underwent ameroid constrictor placement to the left circumflex coronary artery to simulate chronic ischemia. Seven weeks after ameroid placement, all animals underwent hemodynamic and functional measurements followed by cardiac harvest. Both OHC and OHCM animals developed significantly greater weight gain, total cholesterol, and LDL:HDL ratio compared to OC controls. Metformin administration reversed diet-induced hypertension and glucose intolerance. There were no differences in global and regional contractility, myocardial perfusion, capillary and arteriolar density, or total protein oxidation between groups. Myocardial protein expression of VEGF, PPAR-α, γ, and δ was significantly increased in the OHC and OHCM groups. Microvessel reactivity was improved in the OHC and OHCM groups compared to controls, and correlated with increased p-eNOS expression. Overfed Ossabaw miniswine develop several components of metabolic syndrome. However, impairments of myocardial function, neovascularization and perfusion were not present, and microvessel reactivity was paradoxically improved in hypercholesterolemic animals. The observed cardioprotection despite metabolic derangements may be due to lipid-dependant upregulation of the PPAR pathway which is anti-inflammatory and governs myocardial fatty acid metabolism.

Cardioprotective effects of red wine and vodka in a model of endothelial dysfunction.

BACKGROUND: Moderate alcohol consumption is largely believed to be cardioprotective, while red wine is hypothesized to offer benefit in part due to the proangiogenic and antioxidant properties of polyphenols. We investigated the cardiovascular effects of both red wine and vodka in a swine model of endothelial dysfunction. METHODS: Twenty-seven male Yorkshire swine fed a high-fat/cholesterol diet were divided into three groups and received either no alcohol (Control), red wine, or vodka. After 7 wk, myocardial perfusion was measured, and ventricular tissue was analyzed for microvascular reactivity and immunohistochemical studies. RESULTS: There were no differences in myocardial perfusion, in arteriolar or capillary density, or in VEGF expression among groups. Total protein oxidation as well as expression of superoxide dismutase-1 and -2 and NADPH oxidase was decreased in both treatment groups compared to controls. Endothelium-dependent microvessel relaxation, however, was significantly improved only in the red wine-supplemented group. CONCLUSIONS: Supplementation with both red wine and vodka decreased oxidative stress by several measures, implicating the effects of ethanol in reducing oxidative stress in the myocardium. However, it was only in the red wine-supplemented group that an improvement in microvessel function was observed. This suggests that a component of red wine, independent of ethanol, possibly a polyphenol such as resveratrol, may confer cardioprotection by normalizing endothelial dysfunction induced by an atherogenic diet.

Development of a risk score to predict occurrence of deep sternal dehiscence requiring operative debridement.

OBJECTIVE: Severe deep sternal wound (DSW) complications after cardiac surgery are a source of cost, morbidity, and mortality. Our objective was to develop and validate a clinical risk score for predicting risk of DSW requiring operative bone debridement, the most severe form of sternal dehiscence. METHODS: A retrospective review was conducted of patients who underwent open cardiac surgery at a single institution between October 2007 and March 2019. Primary outcome was DSW requiring sternal bone debridement. Potential risk factors were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and significant covariates were included in a logistic regression prediction model. Interval validation was performed using 10-fold cross-validation. A novel sternal wound dehiscence risk score was derived from the relative parameterization estimates. RESULTS: One hundred thirty-four of 8403 patients (1.6%) were identified as having a DSW. Female sex (odds ratio [OR], 2.75; 95% CI, 2.58-2.93), body mass index (OR, 1.0946; 95% CI, 1.09-1.09), percent glycated hemoglobin (OR, 1.31; 95% CI, 1.28-1.33), peripheral vascular disease (OR, 2.38; 95% CI, 2.2005-2.5752), smoking (OR, 1.66; 95% CI, 1.53-1.79) and elevated creatinine level (OR, 1.20; 95% CI, 1.18-1.22) were independent predictors of DSW. Patients were categorized as minimal risk (0%-1%), low risk (2%-3%), intermediate risk (4%-7%), and high risk (9%-64.0%) on the basis of risk score. CONCLUSIONS: This risk stratification model for DSW requiring operative debridement might provide individualized estimates of risk, and guide counseling and potential risk mitigation strategies.