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Background Pulsatile perfusion may offer microcirculatory advantages over conventional nonpulsatile perfusion during cardiopulmonary bypass (CPB). Here, we present direct visual evidence of microvascular perfusion and vasoreactivity between perfusion modalities. Methods A prospective, randomized cohort study of 20 high-risk cardiac surgical patients undergoing pulsatile (n = 10) or nonpulsatile (n = 10) flow during CPB was conducted. Changes in sublingual mucosal microcirculation were assessed with orthogonal polarization spectral imaging along with near-infrared spectroscopic indices of thenar muscle tissue oxygen saturation (StO 2 ) and its recovery during a vascular occlusion test at the following time points: baseline (T 0 ), 30 minutes on CPB (T 1 ), 90 minutes on CPB (T 2 ), 1 hour after CPB (T 3 ), and 24 hours after CPB (T 4 ). Results On the basis of our scoring scale, a shift in microcirculatory blood flow occurred over time. The pulsatile group maintained normal perfusion characteristics, whereas the nonpulsatile group exhibited deterioration in perfusion during CPB (T 2 : 74.0% ± 5.6% versus 57.6% ± 5.0%) and after CPB (T 3 : 76.2% ± 2.7% versus 58.9% ± 5.2%, T 4 : 85.7% ± 2.6% versus 69.8% ± 5.9%). Concurrently, no important differences were found between groups in baseline StO 2 and consumption slope at all time points. Reperfusion slope was substantially different between groups 24 hours after CPB (T 4 : 6.1% ± 0.6% versus 3.7% ± 0.5%), indicating improved microvascular responsiveness in the pulsatile group versus the nonpulsatile group. Conclusions Pulsatility generated by the roller pump during CPB improves microcirculatory blood flow and tissue oxygen saturation compared with nonpulsatile flow in high-risk cardiac surgical patients, which may reflect attenuation of the systemic inflammatory response and ischemia–reperfusion injury.

Background The interaction between baseline kidney function and the performance of biomarkers of acute kidney injury (AKI) on the development of AKI is unclear. Study Design Post hoc analysis of prospective cohort study. Setting & Participants The 1,219 TRIBE-AKI Consortium adult cardiac surgery cohort participants. Predictor Unadjusted postoperative urinary biomarkers of AKI measured within 6 hours of surgery. Outcome AKI was defined as AKI Network stage 1 (any AKI) or higher, as well as a doubling of serum creatinine level from the preoperative value or the need for post-operative dialysis (severe AKI). Measurements Stratified analyses by preoperative estimated glomerular filtration rate (eGFR) ≤ 60 versus > 60mL/min/1.73m 2 . Results 180 (42%) patients with preoperative eGFRs≤60mL/min/1.73m 2 developed clinical AKI compared with 246 (31%) of those with eGFRs>60mL/min/1.73m 2 ( P 2 -transformed biomarker concentrations, there was a significant interaction between any AKI and baseline eGFR for interleukin 18 ( P =0.007) and borderline significance for liver-type fatty acid binding protein ( P =0.06). For all biomarkers, the adjusted relative risk (RR) point estimates for the risk for any AKI were higher in those with elevated baseline eGFRs compared with those with eGFRs≤60mL/min/1.73m 2 . However, the difference in magnitude of these risks was low (adjusted RRs were 1.04 [95% CI, 0.99-1.09] and 1.11 [95% CI, 1.07-1.15] for those with preoperative eGFRs≤60mL/min/1.73m 2 and those with higher eGFRs, respectively). Although no biomarker displayed an interaction for baseline eGFR and severe AKI, log 2 -transformed interleukin 18 and kidney injury molecule 1 had significant adjusted RRs for severe AKI in those with and without baseline eGFRs≤60mL/min/1.73m 2 . Limitations Limited numbers of patients with severe AKI and post-operative dialysis. Conclusions The association between early postoperative AKI urinary biomarkers and AKI is modified by preoperative eGFR. The degree of this modification and its impact on the biomarker-AKI association is small across biomarkers. Our findings suggest that distinct biomarker cutoffs for those with and without a preoperative eGFR≤60mL/min/1.73m 2 is not necessary.

Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown.The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: 'none' (no exposure prior to surgery), 'held' (on chronic ACEi/ARB but held on the morning of surgery) or 'continued' (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were 'functional' AKI based upon changes in pre- to postoperative serum creatinine, and 'structural AKI', based upon peak postoperative levels of four urinary biomarkers of kidney injury.Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein).Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted.

OBJECTIVE To test whether or not endotoxin induces a dose-dependent reduction of myocardial contractile dysfunction after a standardized period of myocardial ischemia and reperfusion and whether nitric oxide is involved in this form of myocardial protection. DESIGN Prospective, randomized, controlled animal study. SETTING University research laboratory. SUBJECTS Twenty-five male Sprague-Dawley rats. INTERVENTIONS After anesthesia, the left carotid artery was cannulated under sterile conditions and animals were allowed to recover from surgery for 12 hrs. Sterile saline or increasing doses (2.5, 5, or 10 mg/kg body weight) of endotoxin (Escherichia coli O26:B6; Sigma, Mississauga, Ontario, Canada) were given intravenously (1 mL over 5 mins). In some rats, diaspirin-crosslinked hemoglobin (200 mg/kg) was infused 6 hrs and 60 min before endotoxin infusion (10 mg/kg). Hearts were rapidly excised for retrograde perfusion through the ascending aorta (Langendorff apparatus) 6 hrs later. After baseline data collection, hearts were subjected to global ischemia (30 mins, 37 degrees C [98.6 degrees F]), followed by 30 mins of reperfusion. MEASUREMENTS AND MAIN RESULTS Physiologic variables were recorded 6 hrs after saline and endotoxin infusion. Baseline myocardial systolic contractility and diastolic compliance were assessed, respectively, by left ventricular developed pressure (LVDP) and left ventricular (LV) volume-preload relationships. After 30 min of reperfusion, LVDP recovery and left ventricular end-diastolic pressure were measured. Endotoxin induced LV systolic contractile depression, irrespective of the dose of endotoxin administered. LV diastolic dysfunction varied between different doses of endotoxin administered. On reperfusion, endotoxin produced a dose-dependent improvement of postischemic LVDP recovery: 30+/-6% in sham, 78+/-9% in 2.5 mg/kg, 93+/-8% in 5 mg/kg, and 107+/-10% in 10 mg/kg endotoxin heart. In rats treated with 10 mg/kg endotoxin, diaspirin-crosslinked hemoglobin pretreatment abrogated endotoxin-induced postischemic LVDP recovery improvement (105+/-10% vs. 43+/-7%, p = .01). CONCLUSION Sublethal doses of endotoxin induce in a dose-dependent manner a delayed form of myocardial protection against ischemia. Although free-cell hemoglobin solution abrogates this endotoxin-induced cross-tolerance, we propose that possible mechanisms involved in this form of myocardial protection include nitric oxide pathway activation.

Strategies for myocardial protection in cardiac surgery are directed at the prevention of procedure-induced ischemia/reperfusion injury as well as metabolic resuscitation in acute ischemic syndromes. Postreperfusion myocardial dysfunction remains a significant clinical problem, most importantly in certain high-risk patient groups. The large body of experimental evidence demonstrating a significant role for sodium-hydrogen exchange activation in myocardial ischemia/reperfusion injury suggests that the ability to pharmacologically inhibit the exchanger presents a promising new approach to current myocardial preservation techniques.

Objective: Sodium–hydrogen exchange (NHE) activation is a major mechanism of cardiac injury produced by ischemia and reperfusion. In addition, NHE may mediate the direct effects of hydrogen peroxide (H2O2) in normally perfused hearts. The present study was done to determine whether H2O2 at low concentrations producing mild myocardial depression affects post-ischemic recovery of function and to determine the ability of the NHE inhibitor HOE 642 to modulate this effect. Methods : Isolated Langendorff-perfused rat hearts with a left ventricular balloon inflated to an initial end-diastolic pressure of 5 mmHg were subjected to 90 min of global zero-flow ischemia followed by 60 min reperfusion. In Study 1, hearts were randomized for perfusion with or without H2O2 (20 μM) for 15 min before ischemia and throughout reperfusion. In Study 2, identical experiments were done except that the hearts were pretreated with the NHE inhibitor HOE 642 (5 μM). Function was assessed by determining intraventricular pressures. Results: Recovery of developed pressure in Study 1 after 10 min reperfusion was 60.3±8% of pre-ischemic values in control hearts whereas this was reduced to 29.9±10% in hearts treated with H2O2 ( P

Rapid deceleration injury causing blunt thoracic trauma can result in injury to the thoracic aorta. Rupture of the aortic isthmus is the most common presentation; however, injury can occur more proximally in the arch vessels or the aortic root. We present an unusual case of simultaneous innominate artery disruption with aortic valve rupture after a motor vehicle accident, and we discuss issues surrounding the diagnosis and operative management of this rare, but life-threatening condition.

BackgroundAcute kidney injury (AKI) is a serious complication of cardiac operations for which there remains no specific therapy. Animal data and several observational studies suggest that statins prevent AKI, but the results are not conclusive, and many studies are retrospective in nature.MethodsWe conducted a multicenter prospective cohort study of 625 adult patients undergoing elective cardiac operations. All patients were taking statins andwere grouped according to whether statins were continued or held in the 24 hours before operation. The primary outcome was AKI as defined by a doubling of serum creatinine or dialysis. The secondary outcome was the peak level of several kidney injury biomarkers. The results were adjusted for demographic and clinical factors.ResultsContinuing (vs holding) a statin before operation was not associated with a lower risk of AKI, asdefined by a doubling of serum creatinine or dialysis(adjusted relative risk [RR] 1.09; 95% confidence interval [CI] 0.44, 2.70). However, continuing a statin wasassociated with a lower risk of elevation of the following AKIbiomarkers: urine interleukin-18, urine neutrophil gelatinase-associated lipocalin, urine kidney injury molecule-1, and plasma neutrophil gelatinase-associated lipocalin (adjusted RR 0.34; 95% CI 0.18, 0.62), (adjusted RR 0.41; 95% CI 0.22, 0.76), (adjusted RR 0.37; 95% CI 0.20, 0.76), (adjusted RR 0.62; 95% CI 0.39, 0.98), respectively.ConclusionsStatins may prevent kidney injury after cardiac operations, as evidenced by lower levels of kidney injury biomarkers.

Objective: The aim was to examine the effects of the Na+/H+ exchange inhibitors amiloride and methylisobutyl amiloride (MIA) in buffer perfused rabbit hearts subjected to one hour of normothermic ischaemia (37 °C) followed by reperfusion. Methods: Experiments were carried out in five groups of Langendorff perfused rabbit hearts: (1) control, (2) amiloride, and (3) MIA (agents in both the preischaemic and reperfusion perfusate), (4) amiloride-R and (5) MIA-R (agents added at reperfusion only). Functional evaluation included serial measurement of resting tension, force, rates of ventricular force development and relaxation, and coronary perfusion pressure. Samples of coronary effluent were obtained for creatine kinase assay and hearts were freeze clamped for metabolite assays. Results: Reperfusion resulted in a marked increase in resting tension in group (1) which was statistically significant compared to groups (2) and (3). Groups (2) and (3) also showed significantly improved recovery of ventricular force, rate of force development, and rate of ventricular relaxation. Addition of either agent only during reperfusion failed to produce a significant beneficial effect. There were no significant differences among the groups with respect to postreperfusion creatine kinase release or end reperfusion metabolite levels. Conclusion: This study shows for the first time that both of the Na+/H+ exchange inhibitors amiloride and MIA produce improved recovery of ventricular function in rabbit hearts subjected to ischaemia and reperfusion, although the beneficial effect was not obtained with drug administration at the time of reperfusion only.

The incidental finding of malignant internal thoracic lymph nodes while mobilizing the internal thoracic artery (ITA) for coronary bypass grafting has not to our knowledge been previously reported. The cases of 3 male patients who underwent surgery between January 1990 and January 1993 and in whom malignant lymph nodes were found in the ITA pedicle are reviewed. One individual was found to have metastatic carcinoma of the breast, whereas the other 2 were discovered to have previously undiagnosed lymphomas. After undergoing further relevant investigation and treatment, all 3 patients remain free of recurrent disease 6.8 to 9.8 years after their original cardiac surgery. Primary or metastatic malignancy may be encountered in the course of ITA mobilization for grafting. Abnormally enlarged internal thoracic lymph nodes should be sent for pathologic examination.

Myocardial infarction that is attributed to native coronary artery spasm in the early postoperative phase has rarely been documented. We report three cases of postoperative myocardial infarction secondary to angiographically demonstrated coronary spasm. Native coronary artery spasm is a rare, but important cause of postoperative ischemia and infarction. Suspicious electrocardiographic changes warrant consideration of transesophageal echocardiography to detect unexpected wall motion abnormalities. Established treatments include intravenous or intracoronary infusion of nitroglycerin and calcium channel antagonists, although several new therapeutic agents may also be beneficial. Prompt coronary angiography is the only definitive modality for early diagnosis and targeted treatment.

Myocardial edema and histologic changes consistent with tissue injury are reported in association with sepsis-induced myocardial depression. The objective of the present study was to determine whether, in the absence of shock, such changes (assessed by studying microvascular albumin flux, tissue edema, and morphometry) are prerequisites for the development of contractile dysfunction in sepsis. Sprague-Dawley rats were randomized into groups for either cecal ligation and perforation (CLP) or sham study. Twenty-four hours after entry of animals into the study, their myocardial function was assessed with the Langendorff isolated heart technique. Left-ventricular developed pressure (preload: 5 mm Hg) was reduced in CLP animals (34.9 +/- 3.3 mm Hg, n = 10) as compared with time-matched controls (46.4 +/- 4.0 mm Hg, n = 8, p0.05, unpaired t test). This was associated with a significant reduction in the maximal rate of increase (+ dP/dt(max)) and decrease (-dP/dt(max)) in left ventricular pressure in the CLP group (sham versus CLP, unpaired t test, p0.05). Upon reperfusion, after 30 min of ischemia, left ventricular resting tension was decreased in CLP as compared with sham-treated animals (sham versus CLP, analysis of variance (ANOVA) with repeated measures, p0.05). At 24 h, sepsis was not associated with myocardial edema (wet:dry weight ratio, sham = 4.094 +/- 0.098, n = 10; CLP = 4.185 +/- 0.066, n = 7), and tissue albumin flux was reduced (sham = 194 +/- 27 microliters. h-1. g dry wt-1, n = 10; CLP = 100 +/- 14 microliters. h-1. g dry wt-1, n = 7). In tissue processed for electron microscopy, we found no evidence of tissue injury or edema at either 24 or 48 h after CLP. We conclude that polymicrobial normotensive sepsis causes myocardial contractile depression in the absence of changes in myocardial structure.

The extent to which a preference for less aggressive care explains the lower rate of invasive cardiac services for women and African-Americans is unknown. A prospective observational study of 272 patients admitted to the coronary care unit was conducted at a tertiary referral teaching hospital and a community teaching hospital. In stepwise multivariate analysis, having less than a college education, poor cardiac function, not having undergone a previous cardiac catheterization, being a patient in a nonreferral community hospital, and current smoking were positively associated with a patient's stating that he or she would disagree with a physician's recommendation for a cardiac catheterization. The step-wise multivariate model with cardiac catheterization as the dependent variable indicated that being a patient in a referral medical center, patient willingness to accept a physician's recommendation for a cardiac catheterization, severe heart disease, and having attended high school were predictive. Women did not differ from men in their preference for or receipt of cardiac catheterization. Patients in the coronary care unit with lower levels of education were less likely to undergo cardiac catheterization. This association was only partly explained by less educated patients' being less willing to accept a physician's recommendation to undergo cardiac catheterization.

Background. Na + /H + exchange represents an important mechanism for pH regulation in the cardiac cell that, however, may paradoxically mediate tissue damage in the reperfused myocardium. We investigated whether inhibition of the exchanger can protect the heart against damage after prolonged hypothermic storage with the use of the selective inhibitor 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694). Methods. After equilibration, isolated rabbit hearts were arrested with a 3 minute infusion of modified St. Thomas' cardioplegic solution and subsequently maintained in ischemic arrest at 4°C for 12 hours before reperfusion at 37°C for 60 minutes. Left ventricular function and creatine kinase release were measured at intervals throughout reperfusion. High-energy phosphate and adenine nucleotide content were determined in hearts before cardioplegia, at the end of the 12-hour storage period, and at the end of reperfusion. HOE 694 (1 μmol/L) was administered either with cardioplegia and throughout reperfusion (study 1) or selectively with either cardioplegia or reperfusion only (study 2). Results. In study 1, systolic function in untreated hearts recovered to less than 40% of preischemic values and was associated with a greater than 1,000% percent sustained elevation in left ventricular end-diastolic pressure. In contrast, systolic recovery in HOE 694-treated hearts was significantly accelerated and improved to approximately 80%, whereas left ventricular end-diastolic pressure increased to only 300% of baseline. Significant protection also occurred in those hearts in which HOE 694 was administered only at reperfusion while the drug was less effective if given only during cardioplegia. Creatine kinase release was not significantly affected except in study 2, where it was significantly lower after 60 minutes of reperfusion in hearts where HOE 694 was added at the time of reperfusion. Tissue metabolite content was not affected by drug treatment. Conclusions. This study shows a marked protective effect of the Na + /H + exchange inhibitor HOE 694 in rabbit hearts subjected to 12 hours of hypothermic ischemia and strongly suggests that antiport inhibitors could play an effective role in myocardial preservation.

Rupture of cardiac chambers after nonpenetrating blunt thoracic trauma is being recognized with increasing frequency. Despite a high mortality rate, survival after repair of a single-chamber rupture is widely reported. Bichamber cardiac rupture is less frequent, and we report a patient who survived this injury.

Cardiopulmonary bypass is known to cause neutrophil activation, and activated neutrophils appear to be of importance in myocardial reperfusion injury. This study examined the effect of a preischemic infusion of activated neutrophils on the recovery of myocardial function after 40 minutes of hypothermic global ischemia. Studies were carried out in three groups of Langendorff-perfused rabbit hearts: control, control (unactivated) neutrophil infusion, and phorbol myristate acetate-activated neutrophil infusion. The activated neutrophil group showed significant deterioration in function during the activated neutrophil infusion. All three groups demonstrated significant depression of function initially after reperfusion, but the two control groups subsequently recovered to baseline levels. The activated neutrophil group, however, showed a persistent significant depression in ventricular force, rate of ventricular tension development, and rate of ventricular relaxation as well as a significant increase in coronary vascular resistance. It is concluded that activated neutrophils depress myocardial function and contribute to impaired recovery of function after global hypothermic ischemia.

Although use of the internal thoracic artery (ITA) for coronary artery bypass grafting results in superior graft patency and improved patient survival, our initial clinical observations suggested an increased incidence of pleuropulmonary morbidity with its use. One hundred consecutive patients with left ITA grafts were studied prospectively and compared with a consecutive retrospective group of 100 patients undergoing coronary artery bypass grafting with saphenous vein grafts only. Preoperative, postoperative day (POD) 2, POD 6, and postoperative week 8 chest roentgenograms were analyzed for atelectasis and effusion. Postoperative left lower lobe atelectasis was common in both groups on both POD 2 (saphenous vein, 43%, versus ITA, 53%; not significant) and POD 6 (saphenous vein, 40%, versus ITA, 41%; not significant). There was a significantly higher incidence of pleural effusion on POD 6 in the ITA group (84% versus 47%; p less than 0.05) but most of these were small. There was more chest tube drainage (1,413 versus 1,028 mL; p less than 0.01) and a greater need for secondary thoracostomy or thoracentesis (4% versus 0%) in the ITA group. The left pleural space was opened in 67 of the 100 ITA patients but pleurotomy did not appear to influence postoperative morbidity. We conclude that use of the internal thoracic artery for coronary artery bypass grafting results in a small but significant increase in pleuropulmonary morbidity.

Myocardial reperfusion after brief, reversible ischemia is frequently associated with malignant arrhythmias in experimental animals. These observations have been extrapolated to humans despite being restricted to anesthetized, open chest preparations. No data are available regarding the incidence of reperfusion arrhythmias after reversible (less than 20 minutes) ischemia in the conscious state. Thus, reperfusion arrhythmias after a 15 minute occlusion of the left anterior descending coronary artery were compared in 24 open chest dogs (17 anesthetized with pentobarbital and 7 with chloralose plus urethane) and 25 conscious, unsedated, trained dogs. The incidence of all rhythm disorders (single premature ventricular complexes, pairs, ventricular tachycardia and fibrillation) was markedly and significantly lower in conscious than in either pentobarbital- or chloralose-anesthetized dogs. The disparity was not accounted for by differences in coronary collateral flow, coronary reactive hyperemia or occluded bed size. The conscious animals, however, exhibited lower heart rates and arterial pressures during reperfusion than did the open chest dogs, suggesting a lower level of adrenergic stimulation, which might have contributed to the reduced incidence of reperfusion arrhythmias. Coronary reperfusion after 15 minutes of occlusion is unlikely to precipitate ventricular tachyarrhythmias in the conscious, trained dog, even after severe ischemia. The occurrence of these rhythm disorders in anesthetized models may reflect the influence of surgical trauma or excessive adrenergic activity, or both. Reperfusion arrhythmias after reversible ischemia may be considerably less common in the clinical setting than previously postulated on the basis of open chest animal experiments.

Conventional measurement of wall thickening with two transit-time crystals requires considerable skill, is associated with myocardial trauma, and does not discern the function of different layers of the left ventricular (LV) wall. To overcome these limitations, we have developed a 10 MHz pulsed Doppler technique that measures thickening at any depth of the LV wall from a single crystal sutured to the epicardium. To verify its accuracy, we compared measurements of thickening fraction (TF) by pulsed Doppler and transit-time methods in 25 open-chest dogs. The epicardial Doppler crystal was placed over an intramyocardial crystal positioned either in the subendocardium or midwall. The epicardial crystal acted as both the Doppler transducer and the transit-time transmitter, so that TF was measured by each technique at the same site. A wide range of regional function (transmural TF:-28-42%, epicardial TF:-20-28%) was produced by coronary occlusion followed by reperfusion, and by isoproterenol and phenylephrine infusions. There was a good correlation between the two methods, both for transmural TF (r = 0.98, 107 paired measurements) and epicardial TF (r = 0.99, 70 paired measurements). Despite marked changes in function, the two techniques yielded similar measurements under all of the conditions tested (base line, ischemia, 5, 15, 30, 60, 120, and 180 min of reperfusion, isoproterenol and phenylephrine). One-millimeter errors in selecting the depth of the Doppler sample volume did not significantly affect the accuracy of TF measurements. Thus the single pulsed Doppler crystal provides a simple, atraumatic, and accurate means for measuring myocardial function, both transmurally and in selected layers of the LV wall.

Between July 1979 and December 1984, 785 patients received 815 St. Jude Medical valve prostheses. Valve-related mortality in the follow-up period was due to thromboemholism in seven cases, anticoagulant-related hemorrhage in three and perivalvular leak in two. Freedom from valve-related death or reoperation at 3 years was 96.4% for aortic valve replacement and 98.3% for mitral valve replacement. The overall rate of thromboembolism was 2.6%/patient-year with warfarin, 9.2%/patient-year with antiplatelet medication and 15.6%/patient-year in patients with no anticoagulant therapy. One episode of thrombotic obstruction of a mitral valve, in a patient receiving no anticoagulant therapy, resulted in an occurrence rate of such obstruction of 0.22%/patient-year. Valve replacement with the St. Jude valve produced excellent clinical results, but long-term anticoagulation with warfarin was required to minimize thromboembolic complications. The use of antiplatelet agents alone provided inadequate protection.

The prolonged myocardial dysfunction observed after reversible ischemia (stunned myocardium) has been postulated to result from an inability of the myocytes to replenish ATP stores. Accordingly, one would expect inotropic stimulation to result in minimal increase in contractile function, or possibly even further deterioration. To test this hypothesis, studies were performed in open-chest dogs undergoing a 15-minute occlusion of the left anterior descending coronary artery (LAD) followed by 4 hours of reperfusion. Systolic wall thickening, an index of regional myocardial function, was measured in the LAD-dependent territory with ultrasonic crystals. Thickening fraction was 20.8 +/- 3.0% (mean +/- standard error of the mean) under baseline conditions, decreased to -18.6 +/- 1.6% during LAD occlusion, and was still severely depressed after 3 hours of reperfusion (2.6 +/- 3.4%). Thickening fraction remained stable between 3 and 4 hours of reperfusion in 5 untreated control dogs. In 9 treated dogs, isoproterenol (0.1 microgram/kg/min intravenously for 30 minutes starting 3 hours after reperfusion) increased thickening fraction to values (24.8 +/- 4.5%) that were similar to those at baseline. Thirty minutes after discontinuation of isoproterenol administration, thickening fraction had returned to pre-isoproterenol levels. Thus, reperfused, severely depressed myocardium responds dramatically to beta-adrenergic stimulation without subsequent adverse effects on function in the short-term. These findings imply that the stunned myocardium can generate ATP, and therefore do not support the view that an inability to replenish ATP stores is the cause of postischemic dysfunction. More important, this study suggests that postischemic dysfunction in humans may be effectively reversed with inotropic therapy without short-term deleterious sequelae.

Recent evidence suggests that postischemic myocardial dysfunction (or myocardial “stunning”) may be mediated by oxygen free radicals, but the mechanism for their production remains unknown. To explore the role of xanthine oxidase as a potential source of free radicals, open-chest dogs undergoing a 15-min occlusion of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion (REP) received intravenously either allopurinol (50 mg/kg 48 h, 20 h, and 30 min before occlusion, 10 mg/kg 1 min before REP, and 6.25 mg X kg-1 X h-1 throughout REP, n = 13) or saline (n = 14). The two groups were similar with respect to occluded bed size (postmortem perfusion) and collateral flow (radioactive microspheres). In controls, the transcardiac difference in plasma uric acid (great cardiac vein - arterial concentration) increased 199 +/- 70% (means +/- SE) during ischemia (P less than 0.02) and remained elevated for 5 min after REP; no increase was observed in treated dogs. Regional myocardial function was assessed by measuring systolic wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under base-line conditions and similar degrees of dyskinesis during ischemia. Following REP, however, recovery of contractile function (expressed as percent of preocclusion values) was considerably greater in allopurinol-treated as compared with control dogs: 57 +/- 14 vs. -22 +/- 16 (P less than 0.01) at 1 h, 70 +/- 13 vs. -15 +/- 15 (P less than 0.001) at 2 h, 65 +/- 14 vs. -28 +/- 13 (P less than 0.001) at 3 h, and 68 +/- 13 vs. -17 +/- 14 (P less than 0.001) at 4 h. These differences could not be ascribed to hemodynamic factors. The results suggest that xanthine oxidase is a source of the oxygen free radicals responsible for myocardial stunning following a brief episode of reversible regional ischemia.

Myocardial reperfusion after reversible regional ischemia is known to result in delayed recovery of contractile function, but the mechanism responsible for this phenomenon remains unclear. We examined the ability of N-2-mercaptopropionylglycine, a synthetic thiol compound with oxygen free radical scavenging properties, to attenuate postischemic dysfunction in open chest dogs undergoing a 15 minute occlusion of the left anterior descending coronary artery followed by 4 hours of re-perfusion. Treated animals received an infusion of N-2-mercaptopropionylglycine (50 mg/kg per h) for 4 hours starting 15 minutes before coronary occlusion. Collateral flow, as determined with radioactive microspheres after 10 minutes of ischemia, was 0.07 ± 0.01 ml/min per g (mean ± SE) in both control (n = 20) and treated (n = 13) groups. The occluded vascular bed, as determined by postmortem perfusion, averaged 26.1 ± 1.2% of the weight of the left ventricle in control and 29.6 ± 1.3% in treated animals.Systolic wall thickening (an index of regional function) was assessed with an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesia during ischemia. Nevertheless, recovery of function (expressed as percent of baseline) was considerably greater in the treated dogs at 1 hour (44.6 versus 12.8%, p = 0.05), 2 hours (64.0 versus 31.6%, p < 0.02), 3 hours (77.1 versus 36.7%, p < 0.01) and 4 hours of reperfusion (75.0 versus 40.0%, p < 0.05).Thus, N-2-mercaptopropionylglycine produced a significant and sustained improvement in recovery of contractile function after a brief episode of regional myocardial ischemia. These results suggest that oxygen free radicals play a significant role in myocardial postishemic dysfunction. Because N-2-mercaptopropionylgly-cine is potentially available for oral prophylactic therapy, these results have significant therapeutic implications.

We examined biventricular function in patients with the adult respiratory distress syndrome (ARDS) by a combination of invasively determined pressures and flows and concomitant radionuclide angiography. Right (RVEF) and left (LVEF) ventricular ejection fractions were measured; right and left ventricular end-diastolic (EDVI) and end-systolic (ESVI) volume indices were calculated from the respective ejection fraction and measured thermodilution stroke volume. With an increase in the outflow pressure load on the right ventricle, measured as the mean pulmonary artery pressure (PAP), the RVEF fell (Y = 66.25 -1.01X; r2 = .42; p less than .001) and both the RVEDVI (y = 13.39 + 3.66X; r2 = .33; p less than .001) and RVESVI (Y = 23.9 + 3.57X; r2 = .41; p less than .001) increased. Progressive increases in the PAP also seemed associated with a change in left ventricular end-diastolic pressure-volume relationships: without pulmonary artery hypertension (PAP less than 20 mm Hg) the mean LVEDVI was 87.2 +/- 31.3 ml/m2 (mean +/- SD) and the mean PCWP was 5.0 +/- 2.8 mm Hg; with a mean PAP exceeding 30 mm Hg, the LVEDVI remained constant (90.4 +/- 26.9 ml/m2) although the PCWP was greater than previous (18.5 +/- 5.7 mm Hg; p less than .01). Analysis of right ventricular peak-systolic pressure end-systolic volume ratios implied a concurrent depression in right ventricular contractility at high levels of PAP. However, right ventricular "pump" function to maintain an adequate left ventricular preload remained unaltered regardless of the presence of pulmonary artery hypertension.