Citric Acid Cycle Metabolites Predict the Severity of Myocardial Stunning and Mortality in Newborn Pigs.

OBJECTIVES: Myocardial infarction and chronic heart failure induce specific metabolic changes in the neonatal myocardium that are closely correlated to outcome. The aim of this study was to examine the metabolic responses to noninfarct heart failure and inotropic treatments in the newborn heart, which so far are undetermined. DESIGN: A total of 28 newborn pigs were instrumented with a microdialysis catheter in the right ventricle, and intercellular citric acid cycle intermediates and adenosine metabolite concentrations were determined at 20-minute intervals. Stunning was induced by 10 cycles of 3 minutes of ischemia, which was performed by occluding the right coronary artery, followed by 3 minutes of reperfusion. Animals were randomized for treatment with epinephrine + milrinone, dopamine + milrinone, dobutamine, or saline. SETTING: University hospital animal laboratory. MAIN RESULTS: Ischemia-reperfusion induced right ventricular stunning and increased the concentrations of pyruvate lactate, succinate, malate, hypoxanthine, and xanthine (all, p < 0.01). During inotrope infusion, no differences in metabolite concentrations were detected between the treatment groups. In nonsurviving animals (n = 8), concentrations of succinate (p < 0.0001), malate (p = 0.009), and hypoxanthine (p = 0.04) increased compared with survivors, while contractility was significantly reduced (p = 0.03). CONCLUSIONS: Accumulation of citric acid cycle intermediates and adenosine metabolites reflects the presence of myocardial stunning and predicts mortality in acute noninfarct right ventricular heart failure in newborn pigs. This phenomenon occurs independently of the type of inotrope, suggesting that citric acid cycle intermediates represent potential markers of acute noninfarct heart failure.

Clinical characteristics and outcomes of neurogenic stress cadiomyopathy in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is an often devastating form of stroke. Aside from the initial hemorrhage, cardiac complications can occur resulting in neurogenic stress cardiomyopathy (NCM), leading to impaired cardiac function. We investigated whether aSAH patients with NCM had poorer long term functional outcomes than patients without NCM. Mortality, vasospasm, and delayed ischemic complications were also evaluated. METHODS: A retrospective study of all patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) from January 2006 to June 2011 (n=299) was conducted. Those patients who underwent an echocardiogram were identified (n=120) and were assigned to the NCM (n=49) category based on echocardiographic findings defined by a depressed ejection fraction (EF%) along with a regional wall motion abnormality (RWMA) in a non-vascular pattern. Primary outcome measures included in-hospital mortality and functional outcomes as measured by the Modified Barthel Index (mBI) at 3 months and one year. Secondary analysis determined if there was an association between NCM, cerebral vasospasm and delayed cerebral ischemia. RESULTS: 16% of aSAH patients developed NCM. Mortality was higher (p<.001) in the NCM group (n=23[46.9%]) than in the non-CM group (n=28[11.2%]). Patients with NCM had poorer functional outcomes as measured by the mBI at both 3 months (p=.002) and 12 months (p=.014). The Hunt-Hess score was predictive of functional outcome as measured by the mBI at both 3 months (p=.002) as well as at 1 year (p=.014). NCM was associated with both death (p=.047 CI, 1.012-7.288) and vasospasm (p=.008 CI, 1.34-6.66) after correction for Hunt-Hess grade. Tobacco use (p<.001) and a history of diabetes mellitus (p<.009) were also associated with vasospasm. NCM was associated with higher in-hospital mortality (p=.047) in multivariate analysis. CONCLUSION: NCM is seen in a substantial number of aSAH patients and when present, it is associated with higher mortality and poorer long-term functional outcomes. This finding may guide further prospective studies in order to determine if early recognition of NCM as well as optimization of cardiac output would improve mortality.

Preadmission beta-blockers are associated with decreased incidence of neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Neurogenic stunned myocardium (NSM) is a frequent complication of aneurysmal subarachnoid hemorrhage (aSAH), with a significant impact on disease course. The presumed cause is catecholamine surge at the time of aneurysm rupture. Beta-blockers, which reduce the impact of the catecholamine surge, may decrease the risk of developing NSM. METHODS: A chart review of 234 consecutive patients admitted to the Oregon Health and Science University Neurosurgery service between March 6, 2008 and June 23, 2010 with a diagnosis of aneurysmal SAH was performed. This group was further subdivided by patients who received echocardiograms on admission, by gender, and by the prehospital administration of ß-blockers. RESULTS: One hundred thirty of 234 patients had echocardiograms on or shortly after admission, and 18 of these developed NSM (13.8%). None of the 22 patients taking prehospital ß-blockers developed NSM. Using the Fisher exact test to compare the 2 groups, patients who were administered prehospital ß-blockers were significantly less likely to develop stunning compared to those who were not (P = .04). After correcting for other variables using multiple logistic regression analysis, the previous use of ß-blockers was still found to be significantly associated with a decreased incidence of NSM after SAH (P = .049). There was no significant difference in hospital length of stay, peribleed stroke, vasospasm, or death. Of the 18 patients with stunning, 15 were women, 5 of whom were on estrogen supplementation. The mean peak troponin elevation of women who developed NSM on estrogen supplementation was significantly higher than for those who were not (mean peak troponin 9.97 ± 2.01 mg/dL; P < .001). CONCLUSION: Prehospital ß-blockers are associated with decreased risk of developing NSM in patients with aSAH. Estrogen may play an additional role in shaping the degree of NSM in women.

Early intra-aortic balloon pumping following perioperative myocardial injury improves hospital and mid-term prognosis.

We evaluated the impact of immediate intra-aortic balloon pumping (IABP) on hospital and mid-term outcome of coronary artery bypass graft (CABG) whenever perioperative acute complications developed. We compared clinical, biochemical, echocardiographic in-hospital results and two-year follow-up outcome of 30 low-risk (EuroSCORE<5) CABG (group A) who immediately received perioperative IABP when acute complications were suspected, to a contemporary, uncomplicated case-matched group (30 patients; Group B). Two in-hospital deaths were recorded in group A with no deaths in controls (P=0.492). Group A showed significantly higher lactate only at ICU arrival (P=0.001). Troponin I was always higher, but never reached values diagnostic for myocardial infarction (P<0.001). Worse left ventricular ejection fraction (P<0.001) and wall motion score index (P=0.008) were recorded at ICU arrival in group A, although an almost complete recovery was registered at discharge. Two-year actuarial survival was similar between the two groups (P=0.598). No differences were observed in freedom from acute myocardial infarction (P=0.503) and from overall cardiac complications (P=0.410). Early IABP should be established whenever cardiac complications are suspected, because of its beneficial impact on enzymatic leakage, myocardial recovery at echocardiography, hospital outcome, mid-term follow-up survival and freedom from cardiovascular events.

Preoperative positron emission tomographic viability assessment and perioperative and postoperative risk in patients with advanced ischemic heart disease.

OBJECTIVES: This study sought to investigate whether determination of tissue viability by means of positron emission tomography (PET) before coronary artery bypass graft surgery (CABG) affects clinical outcome with respect to both in-hospital mortality and 1-year survival rate. BACKGROUND: Patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction are at higher risk for perioperative complications associated with CABG. Therefore, the selection of patients who will benefit from CABG is an important clinical issue. METHODS: This study retrospectively evaluated 76 patients with advanced CAD and LV dysfunction (LV ejection fraction < or = 0.35) who were considered candidates for CABG. Thirty-five patients were selected for CABG on the basis of clinical presentation and angiographic data (group A), and 34 of 41 patients were selected according to extent of viable tissue determined by PET (group B) in addition to clinical presentation and angiographic data. RESULTS: There were four in-hospital deaths (11.4%) in group A and none in group B (p = 0.04). After 12 months, the survival rate was 79% in group A and 97% in group B (p = 0.01). Postoperatively, group B patients had a less complicated recovery (p = 0.05). They required lower doses of catecholamines (p = 0.002) and demonstrated a significantly decreased incidence of low output syndrome (p = 0.05). CONCLUSIONS: This retrospective data analysis suggests that selection of patients with impaired LV function on the basis of extent of viability supplementary to clinical and angiographic data may lead to postoperative recovery with a low early mortality and promising short-term survival. Therefore, viability studies permit selection of patients who are at low risk for serious perioperative complications.

Dobutamine prevents both myocardial stunning and phosphocreatine overshoot without affecting ATP level.

Catecholamines can overcome myocardial stunning. However, a previous report on energy metabolism in stunned myocardium during catecholamine infusion was based on the conventional biochemical methods which might affect contractile function. Twenty farm pigs were anesthetized and underwent 15 min coronary artery occlusion and 2 h reperfusion. Ten pigs were given 10 micrograms/kg/min dobutamine from immediately after and throughout the reperfusion (dobutamine group). The other ten pigs were given saline (control group). Phosphorus-31 magnetic resonance spectroscopy and sonomicrometry were done alternately. Dobutamine improved percent segment shortening after reperfusion (control/dobutamine = 3.8%-5.7%/11.7%-13.4%; P < 0.01). At 15 min ischemia, adenosine triphosphate (ATP) decreased (control/dobutamine = 72 +/- 8%/73 +/- 10%, n.s.), and remained depressed after reperfusion in both groups. After reperfusion, phosphocreatine (PCr) returned to and maintained the preischemic value in the dobutamine group, while in the control group, PCr overshoot (112 +/- 5%) was observed. Except for the presence and absence of PCr overshoot, there was no significant difference of ATP and PCr between the two groups, although rate pressure product was significantly higher in the dobutamine group than in the control group. Regional myocardial blood flow after reperfusion was significantly higher in the dobutamine group. Dobutamine may improve "stunning" through effective improvement of energy utilization and production, indicated by the disappearance of PCr overshoot and maintained ATP level.