Neurogenic myocardial dysfunction post craniopharyngioma resection: A diagnostic dilemma.

Endoscopic transsphenoidal resection of craniopharyngioma is a commonly used technique. Cerebral vasospasm may occur in nearly 10% of cases leading to adverse neurological outcomes. Cardiopulmonary dysfunction may be seen in patients with severe vasospasm. The literature describing the occurrence of neurogenic stunned myocardium following craniopharyngioma resection in pediatric patients is very sparse. Here, we describe such a case managed with a combination of milrinone (to relieve vasospasm and improve cardiac pump function), noradrenaline (to obtain target blood pressure), and vasopressin (to control urine output). This case report proposes the treatment plan of neurogenic stunned myocardium following vasospasm in pediatric patients.

Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery.

OBJECTIVE: This study aims to investigate the utility of mesenchymal stem cells (MSCs) applied as an epicardial patch during coronary artery bypass graft (CABG) to target hibernating myocardium; that is, tissue with persistently decreased myocardial function, in a large animal model. METHODS: Hibernating myocardium was induced in juvenile swine (n = 12) using a surgically placed constrictor on the left anterior descending artery, causing stenosis without infarction. After 12 weeks, single-vessel CABG was performed using left internal thoracic artery to left anterior descending artery graft. During CABG, an epicardial patch was applied to the hibernating myocardium region consisting either of MSCs grown onto a polyglactin mesh (n = 6), or sham polyglactin mesh without MSCs (n = 6). Four weeks after CABG and patch placement, cardiac magnetic resonance imaging was performed and cardiac tissue was examined by gross inspection, including coronary dilators for vessel stenosis and patency, electron microscopy, protein assays, and proteomic analysis. RESULTS: CABG + MSC myocardium showed improvement in contractile function (78.24% ± 19.6%) compared with sham patch (39.17% ± 5.57%) during inotropic stimulation (P < .05). Compared with sham patch control, electron microscopy of CABG + MSC myocardium showed improvement in mitochondrial size, number, and morphology; protein analysis similarly showed increases in expression of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor gamma coactivator 1-alpha (0.0022 ± 0.0009 vs 0.023 ± 0.009) (P < .01) along with key components of the electron transport chain, including succinate dehydrogenase (complex II) (0.06 ± 0.02 vs 0.14 ± 0.03) (P < .05) and adenosine triphosphate synthase (complex V) (2.7 ± 0.4 vs 4.2 ± 0.26) (P < .05). CONCLUSIONS: In hibernating myocardium, placement of a stem cell patch during CABG shows promise in improving myocardial function by improving mitochondrial morphology and function.

Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of CoQ10 on Contractile Reserve Following Bypass Surgery.

There is conflicting clinical evidence whether administration of coenzyme Q10 (CoQ10) improves function following coronary artery bypass graft surgery (CABG). Using a swine model of hibernating myocardium, we tested whether daily CoQ10 would improve contractile function by MRI at 4-week post-CABG. Twelve pigs underwent a thoracotomy and had a constrictor placed on the left anterior descending (LAD). At 12 weeks, they underwent off-pump bypass and received daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo. At 4-week post-CABG, circumferential strain measurements in the hibernating LAD region from placebo and CoQ10 groups were not different and increased to a similar extent with dobutamine (-14.7 ± 0.6 versus -14.8 ± 0.1, respectively (NS)). Post-sacrifice, oxidant stress markers were obtained in the mitochondrial isolates and protein carbonyl in the placebo, and CoQ10 groups were 6.14 ± 0.36 and 5.05 ± 0.32 nmol/mg, respectively (NS). In summary, CoQ10 did not improve contractile reserve or reduce oxidant stress at 4-week post-CABG.

Mitochondrial fusion proteins in revascularized hibernating hearts.

BACKGROUND: Hibernating myocardium is characterized by viable yet dysfunctional myocardium secondary to chronic ischemia, with studies demonstrating incomplete early recovery after coronary artery bypass graft (CABG). We tested whether mitochondrial fusion proteins, an indicator of mitochondrial biogenesis, are increased in hibernating myocardium post-CABG. METHODS: A constrictor was placed on the left anterior descending (LAD) artery of nine pigs. Four of these pigs additionally underwent CABG 12 wk later with a left internal mammary artery graft to the LAD distal to the constrictor. Five pigs had a constrictor placed but did not undergo CABG (Hib). Five pigs did not have a constrictor placed (control). Computerized tomography angiography was used to confirm stenosis at the site of constrictor placement and patency of left internal mammary artery grafts. Regional blood flows were determined at baseline and during 40 µg/kg/min dobutamine infusion. Mitochondrial proteins were quantified by Western blot. RESULTS: Blood flow in the LAD region after CABG was lower than remote regions during dobutamine infusion (2.54 ± 0.24 versus 3.46 ± 0.33 mL/min/g; P < 0.05). Electron transport chain proteins were ∼70% lower in Hib compared with those in control and failed to normalize after CABG. Post-CABG, PGC1α nuclear-bound content was increased compared with Hib (9.02 ± 0.48 versus 5.54 ± 0.98 arbitrary units, respectively; P < 0.05), and expression of mitofusins-1 and 2 and optic atrophy-1 more than doubled. CONCLUSIONS: PGC1α and mitochondrial fusion proteins are increased 4 wk post-CABG in hibernating hearts, indicating mitochondrial fusion has begun to occur and signaling early mitochondrial recovery. Future studies should address changes in maximal myocardial oxygen consumption relative to mitochondrial protein expression.

Expression of uncoupling protein-2 remains increased within hibernating myocardium despite successful coronary artery bypass grafting at 4 wk post-revascularization.

BACKGROUND: We have previously shown that mitochondrial uncoupling protein-2 (UCP-2) is increased in a swine model of hibernating myocardium (HM). Although UCP-2 reduces oxidant stress, it can promote inefficiency of the electron transport chain. In this study, we tested whether UCP-2 remains increased in revascularized HM (RHM) after coronary artery bypass grafting (CABG). METHODS: Seven swine underwent thoracotomy with placement of a constrictor on the left anterior descending artery (LAD). Twelve weeks later, a left internal mammary artery graft was placed on the distal LAD. Four weeks post-CABG, computed tomography angiography documented patent grafts and function. At the terminal study, blood flow to the LAD and remote territories were assessed during high dose dobutamine and mitochondria isolated from both regions for analysis. Comparisons were made to a group of swine with HM who underwent constrictor placement without bypass grafting (n = 4). RESULTS: During dobutamine infusion, RHM demonstrated lower blood flows (2.44 ± 0.23 versus 3.43 ± 0.30 mL/min/g; P < 0.05) and reduced wall thickening (33 ± 9% versus 52 ± 13%; P < 0.05) compared with remote regions. RHM had lower respiratory control indices (3.7 ± 0.3 versus 4.3 ± 0.4; P < 0.05) with persistently increased UCP-2 content. CONCLUSIONS: Despite patent grafts, RHM demonstrates a submaximal response to dobutamine infusion and increased mitochondrial UCP-2 expression. These data support the notion that recovery of the mitochondria in RHM is delayed early post-CABG and may contribute to impaired oxygen consumption and contractile reserve during catecholamine challenges.

Recovery of hibernating myocardium: what is the role of surgical revascularization?

Myocardial responses to chronic ischemia represent a continuum of adaptations resulting, over time, in a stress-resistant phenotype. One such adaptation, hibernating myocardium (HM), has increased antioxidant capacity that protects against ischemia-induced oxidative stress. Studies have suggested that revascularization alone may not fully restore cardiac function, highlighting the need for targeted therapies to serve as adjuncts to the innate healing process following revascularization. In our review, we discuss current understanding of HM and the recovery process following surgical revascularization, focusing on animal models of HM to understand implications for human patients.

Stab wound of the heart with unusual sequelae.

A 31-year-old woman was admitted to the emergency department with a stab wound to the heart. She was initially stable but rapidly developed hypotension. While the operating room and staff were in preparation, she underwent pericardiocentesis. She was then rushed to the operating room by the general surgical trauma team, who performed a bilateral anterior thoracotomy to control the bleeding. In the recovery room, the patient was still hypotensive, so cardiothoracic surgery was consulted. An echocardiogram revealed severe hypokinesis of both ventricles. The cardiothoracic surgeons returned her to the operating room and discovered that the anterior pericardium had been completely removed by the trauma team. This had caused the posterior pericardium to form a "bowstring" that almost totally obstructed pulmonary venous return and restricted right ventricular outflow of blood, inducing right-sided heart failure. This pericardial string also strangulated the left atrium posteriorly, forming 2 compartments. We repositioned the patient's heart and implanted ventricular assist devices bilaterally to provide temporary circulatory support. The patient made a good recovery. We suggest that bilateral assist device placement can be beneficial in the recovery of a stunned but otherwise normal heart.

Continued depression of maximal oxygen consumption and mitochondrial proteomic expression despite successful coronary artery bypass grafting in a swine model of hibernation.

OBJECTIVE: Clinical studies indicate incomplete functional recovery of hibernating myocardium after coronary artery bypass grafting. We hypothesized that persistent contractile abnormalities after coronary artery bypass grafting are associated with decreased mitochondrial proteins involving electron transport chain that might limit maximal oxygen consumption. METHODS: Seven pigs with hibernating myocardium underwent off-pump revascularization with left internal thoracic artery to mid left anterior descending artery. At 4 weeks, left internal thoracic artery anastomosis was patent by multidetector computed tomography. Regional function (transthoracic echocardiography) and blood flow (microspheres) were assessed at rest and during high-dose dobutamine (40 µg/[kg · min]). Expression of electron transport chain proteins was analyzed with isobaric tags for relative and absolute quantification. RESULTS: After revascularization, multidetector computed tomography confirmed severe left anterior descending stenosis and patent left internal thoracic artery graft. Regional function and blood flow normalized at rest; however, function in left anterior descending distribution remained depressed relative to remote regions, and myocardial blood flow in that region did not increase normally when challenged with high-work state. Concomitant with reduced maximal blood flow response in left anterior descending region was more than 40% reduction in electron transport chain proteins essential to adenosine triphosphate production. CONCLUSIONS: Despite successful revascularization of hibernating myocardium, regional function and blood flow remained depressed during catecholamine stress. Electron transport chain proteins known to be downregulated during adaptive process within hibernating myocardium did not normalize after revascularization. These data demonstrate a potential bioenergetic cause of persistent dysfunction and heart failure within successfully revascularized hibernating myocardium.

Neurogenic stunned myocardium after acute hydrocephalus.

Neurogenic stunned myocardium (NSM) is a syndrome of cardiac stunning after a neurological insult. It is commonly observed after aneurysmal subarachnoid hemorrhage but is increasingly being reported after other neurological events. The underlying mechanism of NSM is believed to be a hypothalamic-mediated sympathetic surge causing weakened cardiac contractility and even direct cardiac myocyte damage. The authors report 2 cases of NSM in pediatric patients after acute hydrocephalus. Both patients experienced severe cardiac dysfunction in the acute phase but ultimately had a good neurological outcome and a full cardiac recovery. The identification, treatment, and outcome in 2 rare pediatric cases of NSM are discussed, and the history of the brain-cardiac connection is reviewed.

Ablation of post-myocardial infarction focal ventricular tachycardia.

In the chronic phase of myocardial infarction, the presence of scar areas allows the development of macro-reentries which become the most frequent mechanism underlying ventricular tachycardia (VT). A focal mechanism has been already described in the presence of scar in animal models or in humans but only during surgery. We report a case of focal automatic VT arising from postinfarction scar fibrosis, successfully mapped and ablated during an electro-physiological procedure.

[Influence of coronary revascularization on chronic ischemic stunning of the conduction system of the heart]. / Influência da revascularização coronária sobre o atordoamento isquémico crónico do sistema de condução cardíaco.

UNLABELLED: About one fourth of patients (pts) with coronary artery disease (CAD) referred for coronary bypass surgery (CABG) exhibits some kind of intraventricular conduction defect (IVCD). OBJECTIVE: To assess CABG influence on the behavior of intraventricular conduction in pts submitted to CABG. MATERIAL AND METHODS: Prospective study of 504 pts with severe CAD (3-vessel and/or left main trunk disease), divided in 2 groups (Gr) - GrA, composed of 252 pts with on-pump CABG, and GrB, with 252 pts submitted to off-pump CABG - whose pts were matched for age, gender, angiographic data, additive Euroscore, prior myocardial infarction, diabetes and hypertension. Other data (GrA vs GrB): nr of bypasses/pt 2.9 vs 2.4 (p<0.01); bypass to LAD 100% vs 100%; complete revascularization 60% vs 60%; left ventricular dysfunction 39% vs 34% (NS). Electrocardiographic study: pre-operative 12-lead ECG (within 72 hrs prior to CABG); post-operative (post-op) continuous ECG monitoring by telemetry (1 lead), including recording of data, until the discharge; post-op 12-lead ECG (up to 24 hrs after CABG), eventually repeated accordingly to the telemetric ECG evolution; ECG recordings were always performed by the same technician, with the same ECG recorder (25 mm/sec; 1 mV=10 mm). Results (GrA vs GrB): 1) Pre-operative IVCD 27% vs 24% (NS). 2) Post-op regression/abolition of IVCD (due to reversion of chronic stunning of the conduction system) 24%vs 28% (NS), occurring shortly (up to 24 hrs) after CABG termination in 95% of cases. IVCD aggravation/new IVCD 9.9% vs 0.8% (p<0.001). 3) Post-op IVCD: global figure 28% (+4.5%) vs 21% (-13%), p>0,05; stable IVCD + aggravated IV conduction 30% vs 18% (p<0.01). Post-op permanent pacing: 2 pts vs 0 pts. CONCLUSIONS: 1) A significant number (at least 24%) of pts with severe CAD and stable IVCD shows chronic ischemic stunning of the IV conduction system, which reverts after CABG. 2) Off-pump CABG (in opposition to on-pump CABG), by assuring a better intra-operative protection of the ventricular septum, promotes an improvement of intraventricular conduction in pts submitted to CABG.

Transplantation of bone marrow-derived stem cells improves myocardial diastolic function: strain rate imaging in a model of hibernating myocardium.

BACKGROUND: The aim of this study was to evaluate the cardioprotective effects of bone marrow-derived stem cells on myocardial compliance in a chronic ischemia model regarding strain rate (SR) parameters during dobutamine stress echocardiography (DSE). METHODS: Ameroid constrictors were placed around the circumflex arteries of 23 domestic pigs to induce chronic vessel occlusions. Fifteen pigs received transendocardially bone marrow derived stem cells, and 8 received placebo injections (a 0.9% solution of NaCl) into the ischemic region. At week 6, the animals were evaluated regarding myocardial fibrosis, neovascularization, apoptosis, and diastolic function during DSE. RESULTS: Stem cell-injected hearts showed significantly less fibrosis, higher ejection fractions, significant neovascularization, and less ventricular dilatation than controls (P < .05). Strain rate imaging revealed improved diastolic function, with higher early diastolic SR values and lower E/Ea ratios compared with controls (P < .05). Early diastolic SR during DSE identifies viable myocardium (extent of fibrosis, r = 0.86, P = .0001). CONCLUSION: The endocardial injection of stem cells improves diastolic function in chronic ischemic myocardium and helps attenuate postinfarction remodeling.

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.

Contrast-enhanced cardiac MRI before coronary artery bypass surgery: impact of myocardial scar extent on bypass flow.

The aim of the study was to relate the extent of myocardial late gadolinium enhancement (LGE) in cardiac MRI to intraoperative graft flow in patients undergoing coronary artery bypass graft (CABG) surgery. Thirty-three CAD patients underwent LGE MRI before surgery using an inversion-recovery GRE sequence (turboFLASH). Intraoperative graft flow in Doppler ultrasonography was compared with the scar extent in each coronary vessel territory. One hundred and fourteen grafts were established supplying 86 of the 99 vessel territories. A significant negative correlation was found between scar extent and graft flow (r = -0.4, p < 0.0001). Flow in grafts to territories with no or small subendocardial scar was significantly higher than in grafts to territories with broad nontransmural or transmural scar (75 +/- 39 vs. 38 +/- 26 cc min(-1); p < 0.0001). In summary, the extent of myocardial scar as defined by contrast-enhanced MRI predicts coronary bypass graft flow. Beyond the probability of functional recovery, preoperative MRI might add value to surgery planning by predicting midterm bypass graft patency.

Metabolism of hibernating myocardium assessed by microdialysis during surgical revascularization: report of a case.

We present an 80-year-old woman with hibernating myocardium in the left anterior descending coronary artery (LAD) territory who underwent surgical revascularization and metabolic evaluation of the dysfunctioning segments by microdialysis (microD) technique. Myocardial lactate, pyruvate, and glucose did not show obvious changes throughout the procedure. Conversely, myocardial glycerol and glutamate concentrations markedly increased early after cardioplegic arrest and subsided after weaning from cardiopulmonary bypass (CPB) and recovery of myocardial function. Intraoperative myocardial microD may add relevant pathophysiologic information on hibernating myocardium undergoing coronary flow restoration and, eventually, improve patient care.

Dobutamine stress echocardiography is highly accurate for the prediction of contractile reserve in the early postoperative period, but may underestimate late recovery in contractile reserve after revascularization of the hibernating myocardium.

OBJECTIVE: We sought to investigate the accuracy of dobutamine stress echocardiography to predict the degree and timing of recovery in resting function and contractile reserve (CR) after revascularization of the hibernating myocardium. METHODS: In all, 24 patients with ischemic cardiomyopathy (ejection fraction < 40%) underwent dobutamine stress echocardiography 1 week before and 6 weeks, 3 months, and 6 months after coronary artery bypass grafting. RESULTS: Recovery rates at 6 weeks, 3 months, and 6 months postoperation were 21%, 33%, and 45% (P < .01) for resting function and 55%, 65%, and 74% (P < .01) for CR. Positive and negative predictive values for recovery of resting function and CR at 6 months postrevascularization were 66% vs 97% (P < .001) and 78% vs 48% (P < .001), respectively. Positive and negative predictive values were both high for recovery of CR at 6 weeks postrevascularization (89% and 78%). CONCLUSIONS: Dobutamine stress echocardiography can predict early recovery in CR postrevascularization with an excellent accuracy but may underestimate the degree of late recovery in CR.

Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death.

OBJECTIVES: The aim of the present study was to objectify the loss of myocytes and the mechanism by which myocytes die in human hibernating myocardium (HHM). BACKGROUND: Intracellular degeneration, reduced cellular protein synthesis, and the replacement fibrosis contribute to structural disintegration of HHM. METHODS: In 14 patients, HHM was diagnosed by dobutamine echocardiography, radionuclide ventriculography, and thallium-201 scintigraphy. Functional recovery was documented by repeating the preoperative clinical investigations three months after successful coronary artery bypass graft surgery (CABG). During CABG, transmural biopsies were taken from the center of HHM regions and studied by electron microscopy, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, reverse transcription-polymerase chain reaction, and Western blotting. Control samples were taken from nondiseased human myocardium. RESULTS: All patients showed significant improvement or normalization of the regional function of HHM. Ubiquitin-related autophagic cell death was evident ultrastructurally by the occurrence of autophagic vacuoles, cellular degeneration, and nuclear disassembly. Ubiquitin-protein complexes were found in 0.03 +/- 0.008% (control: 0%, p < 0.005) of all myocytes. The proteasome 20S subunit/total myocytes were reduced from 63.3 +/- 9.6% in control myocardium to 36.9 +/- 8.4% in HHM. Complement-9, indicating oncosis, was found in only one of 14 biopsies. TUNEL-positive myocytes were 0.002 +/- 0.0003%. Electron microscopy showed apoptotic cells in 3 of 14 samples. However, the bcl-2/bax ratio was significantly reduced. Moreover, caspase-3 messenger ribonucleic acid was 8.5 times upregulated, and caspase-3 was activated. Cell death was absent in controls. CONCLUSIONS: In HHM, ubiquitin-related autophagic cell death and apoptosis cause a loss of myocytes. This plays an important role in progressive tissue damage and causes a reduction of the extent of functional recovery of HHM.