High-Sensitivity Troponin Release Profile After Cardiac Surgery.

BACKGROUND: Postoperative serum troponin levels and perioperative myocardial infarction (MI) rates correlate with mortality and morbidity following cardiac surgery. The objective of this study was to document the release profile of high sensitivity troponin T (hsTnT) following different cardiac operations. METHODS: Patients undergoing one of five different isolated cardiac surgical procedures (eligible preoperative hsTnT <29ng/L, serum creatinine < 0.2mmol/L) were recruited prospectively. Serum hsTnT was measured at 0, 4, 6, 8, 10, 12, 24 and 72hours after the first surgical insult to myocardium, together with daily electrocardiographs. RESULTS: There were 10 patients in the on-pump coronary artery bypass group and 5 each in the remaining groups (off-pump coronary artery bypass, open aortic valve replacement, transcutaneous aortic valve implantation and mitral valve replacement). Five additional patients were excluded due to perioperative MI or renal failure. Median [range] of peak hsTnT was 241[99-566], 64[50-136], 353[307-902], 115[112-275], and 918[604-1166] ng/L, respectively. Operations with the lowest peak hsTnT values peaked earliest (four hours) while those with highest values peaked latest (eight hours). CONCLUSION: After cardiac surgery, the hsTnT profile peaks four to eight hours after the initial surgical insult. The magnitude and timing of the peak correlates to the expected degree of surgically-induced myocardial injury.

Changes of left ventricular mechanics after trans-catheter aortic valve implantation and surgical aortic valve replacement for severe aortic stenosis: A tissue-tracking cardiac magnetic resonance study.

BACKGROUND: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS). The aim of the present study was to assess their changes early and late after trans-catheter aortic valve implantation (TAVI) and surgical aortic valve replacement (AVR) using cardiac magnetic resonance (CMR) tissue-tracking imaging. METHODS: In 59 patients with severe AS undergoing either TAVI (n=35) or surgical AVR (n=24), CMR with late gadolinium enhancement (LGE) imaging was performed before and early post-procedure to evaluate LV function and mass, and presence/extent of LGE. A third CMR scan was performed in 29 patients after a mean follow-up of 15±4months. Tissue-tracking analysis was applied to cine CMR images, to assess LV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strains. RESULTS: The TAVI and surgical AVR groups were similar with respect to baseline (p=0.14) and early post-procedure (p=0.16) LV ejection fraction. However, baseline LV GLS was significantly impaired in TAVI patients compared to surgical AVR patients (p=0.025). Early post-procedure, TAVI resulted in a significant improvement of LV GLS (p=0.003), while a significant worsening of LV GLS was observed early after surgical AVR (p=0.012). At longer term follow-up, both TAVI and surgical AVR groups experienced a significant reduction of LV mass and a significant improvement of LV myocardial mechanics in all the three directions. CONCLUSIONS: Treatment-specific differences in the changes of LV myocardial mechanics early after afterload release by TAVI and surgical AVR are present. Later, both interventions are associated with an improvement of LV myocardial deformation, alongside a regression of LV hypertrophy.

An uncommon anatomy presenting with a common disease.

Coronary artery fistulas are rare anomalous communications, between coronary arteries and cardiac chambers and great vessels. They are often congenital, but usually present in adulthood. They can affect cardiac haemodynamic stability and are thought to predispose patients to heart failure, myocardial ischaemia, myocardial infarction, infective endocarditis, arrythmias and rupture. Herein, a case is discussed where a patient with long-standing stable angina was found to have a coronary artery fistula to the main pulmonary artery and concomitant ischaemic heart disease with a chronically occluded left anterior descending artery, proximal to the fistula. It is thought that the fistula probably predisposed the patient's ischaemic heart disease. He underwent a successful coronary artery bypass grafting plus surgical ligation of the coronary artery fistula. This uncommon coronary artery anomaly, presenting with ischaemic heart disease, a common disease in adulthood, is discussed in the context of current recommedations.

Reduction of post-surgical pericardial adhesions using a pig model.

BACKGROUND: Post-surgical pericardial adhesions pose an increased risk of complications during redo sternotomies. Adhesive tissue formation is a normal response to tissue injury and involves complex patho-physiological processes including the actions of prostaglandins to cause plasma leakage and fibrin formation. The purpose of this study was to assess the ability of two non-steroidal anti-inflammatory agents (Indomethacin and Rofecoxib) and a barrier (Coseal, a polyethylene glycol) to limit adhesion formation following cardiac surgery in a pig model. METHODS: Forty-four piglets were allocated equally to four treatment groups: Group 1: Control, Group 2: intramuscular Indomethacin, Group 3: oral Rofecoxib and Group 4: Coseal sprayed on the heart. A full median sternotomy was performed on each animal and the heart exposed. Adhesions were induced by rubbing tissues with gauze, applying sutures and leaving blood in the pericardial sac before chest closure. Plasma inflammatory markers including prostaglandin E(2) and thromboxane B(2) were measured preoperatively and on Days 2, 5 and 10 after surgery. Eight animals from each group were slaughtered after 12 weeks and 3 after 25 weeks. Adhesions were assessed macroscopically and microscopically. RESULTS: Compared to the Control group, the extent of adhesions was significantly less in all other groups whilst adhesion density was least in the Indomethacin and Coseal groups. Indomethacin and less so Rofecoxib, inhibited the synthesis of prostaglandin E(2) and thromboxane B(2) but there were no significant changes in other inflammatory markers. CONCLUSIONS: We conclude that systemic Indomethacin, and locally applied Coseal are suitable methods to markedly reduce pericardial and retrosternal adhesions.

Glycine-extended gastrin stimulates cell proliferation and migration through a Rho- and ROCK-dependent pathway, not a Rac/Cdc42-dependent pathway.

Both amidated gastrin (Gamide) and glycine-extended gastrin (Ggly) stimulate gastrointestinal cell proliferation and migration. Binding of Gamide to the cholecystokinin-2 receptor activates small GTP-binding proteins of the Rho family (Rho, Rac, and Cdc42), and dominant-negative mutants of Rho or Cdc42 block Gamide-stimulated cell proliferation and survival. In comparison, little is known about the Ggly signaling transduction pathway leading to cell proliferation and migration. The present study examined the roles of the small G proteins Rho, Rac, and Cdc42 in Ggly-induced proliferation and migration of the mouse gastric epithelial cell line IMGE-5. Ggly stimulated the activation of Rho and its downstream effector protein ROCK. The activation of Rho and ROCK mediated Ggly-induced cell proliferation and migration as inhibition of Rho by C3, or ROCK by Y-27632, completely blocked these effects of Ggly. Ggly also stimulated tyrosine phosphorylation of focal adhesion kinase, and stimulation was reversed by addition of C3 and Y-27632. In contrast to the effects of Rho and ROCK, inhibition of the Rac or Cdc42 pathways by expression of dominant-negative mutants of Rac or Cdc42 did not affect Ggly-induced cell proliferation and migration. These results demonstrate that Ggly stimulates IMGE-5 cell proliferation and migration through a Rho/ROCK-dependent pathway but not via Rac- or Cdc42-dependent pathways.

A novel non-catalytic mechanism employed by the C-terminal Src-homologous kinase to inhibit Src-family kinase activity.

Although C-terminal Src kinase (CSK)-homologous kinase (CHK) is generally believed to inactivate Src-family tyrosine kinases (SFKs) by phosphorylating their consensus C-terminal regulatory tyrosine (Tyr(T)), exactly how CHK inactivates SFKs is not fully understood. Herein, we report that in addition to phosphorylating Tyr(T), CHK can inhibit SFKs by a novel non-catalytic mechanism. First, CHK directly binds to the SFK members Hck, Lyn, and Src to form stable protein complexes. The complex formation is mediated by a non-catalytic Tyr(T)-independent mechanism because it occurs even in the absence of ATP or when Tyr(T) of Hck is replaced by phenylalanine. Second, the non-catalytic CHK-SFK interaction alone is sufficient to inactivate SFKs by inhibiting the catalytic activity of autophosphorylated SFKs. Third, CHK and Src co-localize to specific plasma membrane microdomains of rat brain cells, suggesting that CHK is in close proximity to Src such that it can effectively inactivate Src in vivo. Fourth, native CHK.Src complex exists in rat brain, and recombinant CHK.Hck complex exists in transfected HEK293T cells, implying that CHK forms stable complexes with SFKs in vivo. Taken together, our findings suggest that CHK inactivates SFKs (i) by phosphorylating their Tyr(T) and (ii) by this novel Tyr(T)-independent mechanism involving direct binding of CHK to SFKs. It has been documented that autophosphorylated SFKs can still be active, in some cases even when their Tyr(T) is phosphorylated. Thus, the ability of the Tyr(T)-independent mechanism to suppress the activity of both non-phosphorylated and autophosphorylated SFKs represents a fail-safe measure employed by CHK to down-regulate SFK signaling under all circumstances.

A novel effect of bismuth ions: selective inhibition of the biological activity of glycine-extended gastrin.

Although bismuth salts have been used for over two centuries for the treatment of various gastrointestinal disorders, the mechanism of their therapeutic action remains controversial. Because gastrins bind two trivalent ferric ions with high affinity, and because ferric ions are essential for the biological activity of glycine-extended gastrin 17, we have investigated the hypothesis that trivalent bismuth ions influence the biological activity of gastrins. Binding of bismuth ions to gastrins was measured by fluorescence quenching and NMR spectroscopy. The effects of bismuth ions on gastrin-stimulated biological activities were measured in inositol phosphate, cell proliferation, and cell migration assays. Fluorescence quenching experiments indicated that both glycine-extended and amidated gastrin 17 bound two bismuth ions. The NMR spectral changes observed on addition of bismuth ions revealed that Glu-7 acted as a ligand at the first bismuth ion binding site. In the presence of bismuth ions the ability of glycine-extended gastrin 17 to stimulate inositol phosphate production, cell proliferation, and cell migration was markedly reduced. In contrast, bismuth ions had little effect on the affinity of the CCK-2 receptor for amidated gastrin 17, or on the stimulation of inositol phosphate production by amidated gastrin 17. We conclude that bismuth ions may act, at least in part, by blocking the effects of glycine-extended gastrin 17 on cell proliferation and cell migration in the gastrointestinal tract. This is the first report of a specific inhibitory effect of bismuth ions on the action of a gastrointestinal hormone.