Hyperoxic vasoconstriction of human pulmonary arteries: a novel insight into acute ventricular septal defects.

Objectives. Acute rises in pulmonary artery pressures following postinfarction ventricular septal defects present a challenge. We hypothesised that the abnormally high oxygen content exposure to the pulmonary arteries may be a factor. We investigated the contractile responses of human pulmonary arteries to changes in oxygen tension. Methods. Isometric tension was measured in large and medium sized pulmonary artery rings obtained from lung resections for patients with bronchial carcinoma (n = 30). Fresh rings were mounted in organ baths bubbled under basal conditions with hyperoxic or normoxic gas mixes and the gas tensions varied during the experiment. We studied whether voltage-gated calcium channels and nitric oxide signalling had any role in responses to oxygen changes. Results. Hypoxia caused a net mean relaxation of 18.1% ± 15.5 (P < 0.005) from hyperoxia. Subsequent hyperoxia caused a contraction of 19.2% ± 13.5 (P < 0.005). Arteries maintained in normoxia responded to hyperoxia with a mean constriction of 14.8% ± 3.9 (P < 0.005). Nifedipine inhibited the vasoconstrictive response (P < 0.05) whilst L-NAME had no effect on any hypoxic vasodilatory response. Conclusions. We demonstrate that hyperoxia leads to vasoconstriction in human pulmonary arteries. The mechanism appears to be dependent on voltage-gated calcium channels. Hyperoxic vasoconstriction may contribute to acute rises in pulmonary artery pressures.

Hyperbaric oxygen preconditioning improves myocardial function, reduces length of intensive care stay, and limits complications post coronary artery bypass graft surgery.

OBJECTIVE: The objective of this study was to determine whether preconditioning coronary artery disease (CAD) patients with HBO(2) prior to first-time elective on-pump cardiopulmonary bypass (CPB) coronary artery bypass graft surgery (CABG) leads to improved myocardial left ventricular stroke work (LVSW) post CABG. The primary end point of this study was to demonstrate that preconditioning CAD patients with HBO(2) prior to on-pump CPB CABG leads to a statistically significant (P<.05) improvement in myocardial LVSW 24 h post CABG. METHODS: This randomised control study consisted of 81 (control group=40; HBO(2) group=41) patients who had CABG using CPB. Only the HBO(2) group received HBO(2) preconditioning for two 30-min intervals separated 5 min apart. HBO(2) treatment consisted of 100% oxygen at 2.4 ATA. Pulmonary artery catheters were used to obtain perioperative hemodynamic measurements. All routine perioperative clinical outcomes were recorded. Venous blood was taken pre HBO(2), post HBO(2) (HBO(2) group only), and during the perioperative period for analysis of troponin T. RESULTS: Prior to CPB, the HBO(2) group had significantly lower pulmonary vascular resistance (P=.03). Post CPB, the HBO(2) group had increased stroke volume (P=.01) and LVSW (P=.005). Following CABG, there was a smaller rise in troponin T in HBO(2) group suggesting that HBO(2) preconditioning prior to CABG leads to less postoperative myocardial injury. Post CABG, patients in the HBO(2) group had an 18% (P=.05) reduction in length of stay in the intensive care unit (ICU). Intraoperatively, the HBO(2) group had a 57% reduction in intraoperative blood loss (P=.02). Postoperatively, the HBO(2) group had a reduction in blood loss (11.6%), blood transfusion (34%), low cardiac output syndrome (10.4%), inotrope use (8%), atrial fibrillation (11%), pulmonary complications (12.7%), and wound infections (7.6%). Patients in the HBO(2) group saved US$116.49 per ICU hour. CONCLUSION: This study met its primary end point and demonstrated that preconditioning CAD patients with HBO(2) prior to on-pump CPB CABG was capable of improving LVSW. Additionally, this study also showed that HBO(2) preconditioning prior to CABG reduced myocardial injury, intraoperative blood loss, ICU length of stay, postoperative complications, and saved on cost, post CABG.

Aprotinin in primary cardiac surgery: operative outcome of propensity score-matched study.

BACKGROUND: Some recent multicenter series have questioned the safety of aprotinin in primary cardiac operations. We report a large, single-center experience with aprotinin therapy in primary cardiac operations and discuss the limitations and potential confounders of current treatment strategies. METHODS: We compared myocardial infarction, neurologic events, renal insufficiency, and operative death after first-time coronary or valve procedures, or both, in 3334 patients treated with full-dose aprotinin with 3417 patients not treated with aprotinin who underwent operation between March 1998 and January 2007. Further analysis was performed for 341 propensity score-matched pairs. RESULTS: There were substantial differences between the groups. Aprotinin patients were higher risk on account of older age, unstable symptoms, poor ejection fraction, preoperative hemodynamic support, emergency/urgent operations, and combined coronary/valve operations. Postoperative bleeding and blood product transfusion were considerably reduced in aprotinin patients, as was median duration of mechanical ventilation. Aprotinin was neither a predictor of postoperative myocardial infarction, renal insufficiency, neurologic dysfunction, or operative death. Achieving parity between the groups by propensity score matching eliminated the elevated rates of postoperative renal insufficiency, neurologic dysfunction, and operative death observed in aprotinin patients in the unmatched comparison. These adverse outcomes were evenly distributed between matched groups. Conversely, blood transfusion had univariate associations with all adverse outcome measures. CONCLUSIONS: Full-dose aprotinin use was not associated with myocardial infarction, neurologic dysfunction, renal insufficiency, or death after coronary or valve operations. We observed less postoperative bleeding and blood product transfusion, and early extubation with the use of aprotinin.

Are initial valve operations in octogenarians still high-risk in the current era?

BACKGROUND AND AIM OF THE STUDY: The average age of cardiac patients continues to increase. As more octogenarians undergo surgery during the current era, the outcome of valve surgery was investigated to determine the operative risk in these patients. METHODS: Among 350 patients aged > or = 80 years who had initial surgery between 1998 and 2006, a total of 188 (105 females, 83 males) underwent valve surgery. A prospective analysis was conducted of the collected data. RESULTS: The median age of patients was 82 years (IQR: 81-84 years), and over half of them presented with severe symptoms (NYHA class III/IV; n = 96), controlled heart failure (n = 108), hypertension (n = 101) and coronary artery disease (n = 108). Concomitant coronary artery bypass grafting (CABG) was performed in 89 cases (47%). Perioperative hemodynamic support with inotropes was common (47%). Hospital death after isolated aortic valve replacement (AVR) (n = 89) and mitral valve replacement (MVR) (n = 10) occurred in four patients (4.5%, median additive EuroSCORE 9.0%) and one patient (10%, median additive EuroSCORE 9.8%), respectively. Concomitant CABG led to a doubling of the operative mortality which, for AVR, declined from 5.4% to 3.8% during the latter half of the study period. The median length of stay was 24 h (IQR 21-44 h) in the intensive care unit, and 10 days (IQR 7-14 days) postoperatively. The risk factors for operative mortality were urgent/emergent surgery (HR 3.27, 95% CI 1.12-9.58, p = 0.03), preoperative gastrointestinal disease (HR 3.15, 95% CI 1.12-8.9, p = 0.03), left ventricular ejection fraction <0.30 (HR 4.37, 95% CI 1.29-14.82, p = 0.02), and ischemic time (HR 1.04, 95% CI 1.004-1.07, p = 0.02). CONCLUSION: Elective isolated AVR can be performed with modest operative risk in octogenarians with good left ventricular systolic function. Additional procedures impose long ischemic times and increase the operative risk, as does MVR. Strategies to minimize the complexity and extent of surgery should benefit these patients.

Early and late survival after surgical revascularization for ischemic ventricular fibrillation/tachycardia.

BACKGROUND: Ischemic ventricular fibrillation/tachycardia (VF/VT) treated by myocardial revascularization, often with an implanted cardioverter defibrillator, prevents sudden cardiac death. Early series have suggested that recurrent VF/VT threatens survival even after treatment. As late outcome is unknown, we sought to determine if the early survival benefit is sustained. METHODS: From January 1999 through January 2007, 93 consecutive patients (75 male, 81%) presented with ischemic VF/VT; 21% survived cardiac arrest and underwent coronary artery bypass graft surgery at our institution. We analyzed their early and late survival. RESULTS: Median age was 66 years (range, 44 to 88). Clinical presentation included class III/IV angina (46%), controlled heart failure (43%), prior myocardial infarction (68%), left ventricular ejection fraction less than 0.30 (23%) and 0.30 to 0.50 (35%), left main stem disease (24%), and triple-vessel disease (67%). Surgical revascularization, mostly nonelective (urgent 73%, emergency 7%), was combined with aortic valve replacement in 5 patients and left ventricular pseudoaneurysm repair in 3. Ischemic territories and mean number of diseased coronaries (2.6) corresponded to the grafted territories and average number of grafts (2.5). Operative mortality was 6.5% (n = 6, median EuroSCORE [European System for Cardiac Operative Risk Evaluation] predicted mortality 9). Recurrent VF/VT occurred early postoperatively in 21 patients (24%). All patients had electrophysiologic studies postoperatively and 40% received an implanted cardioverter defibrillator. Of 12 late deaths (16%) at follow-up extending to 8 years, 4 (33%) were due to cardiac causes. Five-year survival was 88%, equivalent to that (83% to 85%) reported for patients with sinus rhythm preoperatively. CONCLUSIONS: Complete myocardial revascularization for ischemic VF/VT yields excellent early and late results; 5-year survival is comparable to that of patients with preoperative sinus rhythm.

Is post-sternotomy percutaneous dilatational tracheostomy a predictor for sternal wound infections?

OBJECTIVE: Early post-sternotomy tracheostomy is not infrequently considered in this era of percutaneous tracheostomy. There is, however, some controversy about its association with sternal wound infections. METHODS: Consecutive patients who had percutaneous tracheostomy following median sternotomy for cardiac operation at our institution from March 1998 through January 2007 were studied, and compared to contemporaneous patients. We identified risk factors for tracheostomy, and investigated the association between percutaneous tracheostomy and deep sternal wound infection (mediastinitis) by multivariate analysis. RESULTS: Of 7002 patients, 100 (1.4%) had percutaneous tracheostomy. The procedure-specific rates were: 8.6% for aortic surgery, 2.7% for mitral valve repair/replacement (MVR), 1.1% for aortic valve replacement (AVR), and 0.9% for coronary artery bypass grafting (CABG). Tracheostomy patients differed vastly from other patients on account of older age, severe symptoms, preoperative support, lower ejection fraction, more comorbidities, more non-elective and complex operations and higher EuroScore. Risk factors for tracheostomy were New York Heart Association class III/IV (OR 6.01, 95% CI 2.28-16.23, p<0.0001), chronic obstructive pulmonary disease (OR 1.84, 95% CI 1.01-3.37, p=0.05), preoperative renal failure (OR 3.57, 95% CI 1.41-9.01, p=0.007), prior stroke (OR 3.08, 95% CI 1.75-5.42, p<0.0001), ejection fraction<0.30% (OR 2.73, 95% CI 1.23-6.07, p=0.01), and bypass time (OR 1.008, 95% CI 1.004-1.012, p<0.0001). The incidences of deep (9% vs 0.7%, p<0.0001) and superficial sternal infections (31% vs 6.5%, p<0.0001) were significantly higher among tracheostomy patients. Multivariate analysis identified percutaneous tracheostomy as a predictor for deep sternal wound infection (OR 3.22, 95% CI 1.14-9.31, p<0.0001). CONCLUSIONS: Tracheostomy, often performed in high-risk patients, may further complicate recovery with sternal wound infections, including mediastinitis, therefore, patients and timing should be carefully selected for post-sternotomy tracheostomy.

Early neurological complications after coronary artery bypass grafting and valve surgery in octogenarians.

OBJECTIVE: To determine the incidence and risk factors for neurological events complicating cardiac surgery, and the implications for operative outcome in octogenarians. METHODS: Of 6791 who underwent primary on-pump CABG and/or valve surgery from 1998 through 2006, 383 were aged > or =80 years. Neurological complications, classified as reversible or permanent, were investigated by head CT scan in patients who did not recover soon after an event. RESULTS: There were more females (47% vs 26%, p<0.0001) among octogenarians (n=383, median age 82 years) than among younger patients (n=6408, median age 66 years). Controlled heart failure, NYHA class III/IV and chronic obstructive pulmonary disease were more prevalent in octogenarians while preoperative myocardial infarction was predominant in younger patients. Octogenarians were at higher operative risk (median EuroScore 6 vs 2, p<0.0001). Operative procedures differed between octogenarians and younger patients (p<0.0001); respective frequencies were 45% vs 77% for CABG, 26% vs 10% for AVR, and 23% vs 6% for AVR+CABG. Mortality was higher for octogenarians (8.9% vs 2.1, p<0.0001). Early neurological complications observed in 3.9% of the entire study population were mostly reversible (3.2%). Age > or =80 years (odds ratio [OR] 2.82, 95% confidence interval [CI] 1.89-4.21, p<0.0001), prior cerebrovascular disease (OR 2.23, 95% CI 1.56-3.18, p<0.0001), AVR+CABG (OR 2.92, 95% CI 1.60-5.33, p<0.0001) and MVR+CABG (OR 4.77, 95% CI 2.10-10.85, p<0.0001) were predictive of neurological complications. More octogenarians experienced neurological events (p<0.0001): overall 12.8% vs 3.4%, reversible 11.5% vs 2.8%, permanent 1.3% vs 0.6%. Among octogenarians, neurological complication was associated with elevated operative mortality (18% vs 8% for those without neurological complication, p=0.03), and prolonged ventilation, intensive care stay and hospitalisation. Predictors of neurological complications in octogenarians were blood and/or blood product transfusion (OR 3.60, 95% CI 1.56-8.32, p=0.003) and NYHA class III/IV (OR 7.6, 95% CI 1.47-39.70, p=0.02). CONCLUSION: Octogenarians undergoing on-pump CABG and/or valve repair/replacement are at higher risk of neurological dysfunction, from which the majority recover fully. The adverse implications for operative mortality and morbidity, however, are profound. Blood product transfusion which has a powerful correlation with neurological complication should be reduced by rigorous haemostasis with parsimonious use of sealants when appropriate.

The impact of symptom severity on cardiac reoperative risk: early referral and reoperation is warranted.

BACKGROUND: Operative mortality is comparatively higher for coronary artery bypass grafting (CABG) or valve reoperations. Studies of reoperative risk have focussed on surgical techniques. We sought to determine the risk and predictors of poor outcome in current practice, and the influence of preoperative symptoms. METHOD: For every redo patient (n=289), we selected the best-matched pair of patients who underwent a primary operation (n=578) between 1998 and 2006. Matching variables were age, gender, left ventricular ejection fraction (LVEF) and type of operation. Poor outcome was defined as operative mortality or major morbidity. RESULT: Median age was 68 (interquartile range 62-73) years and 28% were female for both groups. Severe symptoms and cardiac morbidity dominated the presentation of redo patients. CABG (53%), valve repair/replacement (34%) and combined CABG and valve (12%) were performed with overall operative mortality of 6.6% (median additive EuroScore 7.0) for redo versus 1.6% (median additive EuroScore 4.0) for primary groups (p<.0001). Whereas no significant difference was observed between primary (1.6%) and redo CABG (3.9%, p=.19), valve reoperations had higher operative mortality (9.6% vs 1.5%, p<.0001). Major complications occurred more frequently after redo valve compared to primary valve operations (28% vs 14%, p=.001). Reoperation (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.66-2.42, p=.48) was not a predictor of major adverse event after CABG or valve surgery. Determinants of poor outcome after valve reoperations were New York Heart Association class III/IV (OR 6.86, 95% CI 2.29-12.11, p=.03), duration of extracorporeal circulation (OR 1.17, 95% CI 1.02-1.35, p=.03) and mitral valve replacement (OR 4.07, 95% CI 1.83-36.01, p=.04). The predictors of major adverse events after redo CABG were congestive heart failure (OR 1.85, 95% CI 1.04-8.98, p=.006) chronic obstructive pulmonary disease (OR 17.5, 95% CI 1.87-35.21, p=.05) and interval from prior surgery (OR 1.37, 95% CI 1.09-1.92, p=.01). CONCLUSION: In the current era, redo CABG is nearly as safe as the primary operation. A valve reoperation, on the contrary, is higher risk due, partly, to severe symptoms at presentation. Patients should be referred and operated on early before they develop severe symptoms.

Can hyperbaric oxygen be used as adjunctive heart failure therapy through the induction of endogenous heat shock proteins?

Heart failure (HF) is a chronic condition that is expected to increase in incidence along with increased life expectancy and an aging population. As the incidence of HF increases, the cost to national healthcare budgets is expected to run into the billions. The costs of lost productivity and increased social reliance on state support must also be considered. Recently, acute myocardial infarction (AMI) has come to be seen as the major contributing factor to HF. Although thrombolysis may restore coronary perfusion after an AMI, it may also introduce ischemic reperfusion injury (IRI). In an attempt to ameliorate sustained protein damage caused by IRI, endogenous chaperone proteins known as heat shock proteins (HSPs) are induced as a consequence of the stress of IRI. Recently, hyperbaric oxygen has been shown to induce the production of HSPs in noncardiac tissue, with a resultant protective effect. This current opinion review article suggests a possible role for hyperbaric oxygen, as a technologically modern drug, in augmenting the induction of endogenous HSPs to repair and improve the function of failing hearts that have been damaged by AMI and IRI. In addition, this simple, safe, noninvasive drug may prove useful in easing the economic burden of HF on already overextended health resources.

Hyperbaric oxygen: a novel technology for modulating myocardial schemia-reperfusion via a single drug.

Over the years, the anecdotal medical use of oxygen has demonstrated, in a non-evidence-based manner, that it may have wide-ranging clinical consequences. Although oxygen is a critical substrate in the alleviation of hypoxia, anoxia, and ischemia, paradoxically, it also functions as a deleterious metabolite during the reperfusion of previously ischemic tissues. In adding to this controversy, a spate of new pioneering work has identified hyperoxygenation (hyperoxia) and its metabolites as solely and purposefully demonstrating cellular and clinical benefit,particularly in the field of ischemic reperfusion injury (IRI). Furthermore, the beneficial effects of oxygen have been technologically augmented by administration at doses above atmospheric pressure and at higher concentrations. The novel technology that involves oxygen treatment at supra-atmospheric pressures in high concentrations is known as hyperbaric oxygen (HBO). Although the concept of hyperbaric oxygen has been around since the mid 20th century, it is only during the past decade or so that its therapeutic potential as a new technology-based drug has been exploited for the purposes of cellular tolerance and protection. HBO has recently been shown to be a useful adjunct in several models of IRI, including myocardial infarction. How it does this remains to be elucidated. This article attempts to bring into the spotlight some pertinent developments regarding HBO and myocardial IRI, while simultaneously stimulating intellect, thought, and discussion as to whether this novel technology--HBO--which consists of only a singular drug--oxygen--is a therapy that warrants further laboratory and clinical investigation as a therapeutic modality that may be safe and cost-effective, without producing significant adverse effects.

Hyperbaric oxygen: a new drug in myocardial revascularization and protection?

Ischemia-reperfusion injury (IRI) occurs following coronary artery revascularization. Reactive oxygen species (ROS) were initially thought to play a role in the pathogenesis of this injury. However, the evidence for this is inconclusive. Recent studies involving ischemic preconditioning have identified ROS as potential mediators for the cardioprotective effects observed following this technique. Furthermore, cardiac studies involving IRI and the use of hyperbaric oxygen (HBO) have demonstrated the ability of HBO to induce cardioprotection and to attenuate IRI. This review suggests the possible role for HBO as a new drug in the arena of myocardial revascularization and cellular protection. While there is mounting clinical evidence for this, a methodological understanding of HBO's cellular mechanisms of actions appears to be lacking. As such, this article attempts to draw the similarity between HBO and other protective oxidative stress mechanisms and then to speculate in an evidence-based manner its possible cellular mechanistic role as a drug via the generation of ROS.

Randomized comparison of stentless versus stented valves for aortic stenosis: effects on left ventricular mass.

BACKGROUND: Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve. We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. METHODS AND RESULTS: The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus < or =25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176+/-62 and 182+/-63 g/m2, respectively) or at 6 months (142+/-49 and 131+/-45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. CONCLUSIONS: Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months.