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The human saphenous vein (HSV) is the most widely used graft in coronary artery revascularization procedures and is susceptible to spasm perioperatively. The aim of this study is to elucidate the mechanism(s) of agonist-induced excitation-contraction coupling in this vessel. Isomerric contraction experiments were combined with in situ smooth muscle intracellular [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]) imaging by confocal microscopy of intact undistended HSV segments during activation with phenylephrine (PE; 50 [micro]M). Stimulation with PE produced a sustained contraction. Pre-incubation with 5 [micro]M nifedipine, a blocker of the L-type voltage-operated [Ca.sup.2+] channel, or 50 [micro]M SKF-96365, a blocker of both the voltage- and receptor-operated channels, reduced force generation by 25-30%. [Ca.sup.2+] imaging revealed that PE elicited only a transient rise in [[[Ca.sup.2+]].sub.i], suggesting that [Ca.sup.2+] plays only a minor role. However, a requirement for basal [Ca.sup.2+] levels was demonstrated when PE contractions could not be maintained in [Ca.sup.2+]-free medium. In light of the transient [Ca.sup.2+] response, it appears that signals other than [Ca.sup.2+] must maintain the tonic contraction elicited by PE, such as those that sensitize the myofilaments to [Ca.sup.2+]. Application of HA-1077 (a Rho kinase inhibitor) at the peak of the contraction completely abolished the plateau phase of the response, whereas application of genistein (a tyrosine kinase inhibitor) reduced this phase by ~50%. The foregoing results suggest that, whereas the transient [Ca.sup.2+] signal can contribute to the development of force, maintenance of the plateau phase of the PE contraction in the HSV is the result of myofilament [Ca.sup.2+] sensitization by Rho kinase and tyrosine phosphorylation. The elucidation of the mechanisms of excitation-contraction coupling in the HSV may be useful for the development of therapeutic strategies for the alleviation of vein graft spasm. calcium; Rho kinase; tyrosine kinase; smooth muscle; [[alpha].sub.1]-adrenergic receptor agonist

A 58-year-old immunocompetent patient with previous prosthetic valve presented with chest pain, constitutional symptoms and septic shock. Blood cultures and transthoracic echocardiogram were negative, but the patient was initiated on broad spectrum antibiotics due to high clinical suspicions of infective endocarditis. The patient received a transoesophageal echocardiogram revealing a cystic bioprosthetic valve lesion. Culturenegative endocarditis workup identified active disseminated histoplasmosis with likely Histoplasma endocarditis. A multidisciplinary discussion was held, and the patient was deemed high-risk for a third re-do open heart surgery. He was treated medically with anti-fungal treatment with good clinical recovery. [ABSTRACT FROM AUTHOR]

Patients with diabetes experience increased cardiovascular complications after cardiac surgery. Hyperglycaemia predicts increased mortality after myocardial infarction and may influence cardiovascular risk in humans. Impaired prosurvival phosphatase and tensin homologue on chromosome 10 (PTEN)-Akt signalling could be an important feature of the diabetic heart rendering it resistant to preconditioning. This study was designed to evaluate for differences and relationships of myocardial PTEN-Akt-related signalling and baseline glycaemic control marker in type 2 diabetic and nondiabetic patients undergoing coronary artery bypass surgery. Right atrial biopsies and coronary sinus blood were obtained from 18 type 2 diabetic and 18 nondiabetic patients intraoperatively. Expression and phosphorylation of Akt, endothelial nitric oxide synthase (eNOS), Bcl-2 and PTEN were evaluated by Western blot. Plasma 15-F-isoprostane concentrations were evaluated by liquid chromatography-mass spectrometry. PTEN expression and 15-F-isoprostane concentrations were significantly higher in diabetic patients. Increased fasting blood glucose levels correlated with increased coronary sinus plasma 15-F-isoprostane concentrations. Increased cardiac 15-F-isoprostane generation was highly correlated with myocardial PTEN expression. Bcl-2 expression and eNOS phosphorylation were significantly lower in diabetic compared with nondiabetic patients. Akt phosphorylation tended to be lower in diabetic patients; however, this tendency failed to reach statistical significance. The current results suggest that prosurvival PTEN-Akt signalling is impaired in the diseased diabetic myocardium. Hyperglycaemia and increased oxidative stress may contribute to this phenomenon. These findings strengthen the understanding of the underlying biologic mechanisms of cardiac injury in diabetic patients, which could facilitate development of new treatments to prevent cardiovascular complications in this high-risk population. [ABSTRACT FROM AUTHOR]

We hypothesized that β-adrenergic stimulation with isoproterenol during continuous normothermic cardioplegic arrest would enhance the regenerative and regulatory function of the myocardium, resulting in improved cardiac function. We studied isolated rabbit hearts paced at ~200 beats per minute (bpm) and perfused by a support rabbit. We measured ventricular pressure over a range of ventricular volumes to determine maximal elastance (E[sub max]) at baseline and 20 and 45 min after discontinuation of cardioplegia. Myocardial oxygen consumption (MVO[sub 2]) measurements were performed simultaneously and during cardioplegic arrest. Hearts were prospectively randomized to receive either isoproterenol at 0.1 M or control in blinded fashion for 10 min during a 1-h continuous warm-blood cardioplegic arrest. Compared to control hearts, isoproterenol-treated hearts had trends toward longer time to first spontaneous heartbeat (control 141 ± 43 vs. isoproterenol 200 ± 74 s, p = .07), and longer time to capture of atrial pacing (control 214 ± 52 vs. isoproterenol 288 ± 91 s, p = .06). There was no difference observed in the MVO[sub 2] between isoproterenol-treated and control groups of hearts. MVO[sub 2] decreased during cardioplegia (p < .01), but there was no significant change in MVO[sub 2] during isoproterenol infusion during cardioplegic arrest. There was a significant reduction in E[sub max] compared to baseline 20 min after discontinuation of cardioplegic arrest in both groups (control 7.3 ± 1.7 mm Hg/μL vs. 9.0 ± 1.7 mm Hg/μL, p = .02, isoproterenol-treated 6.8 ± 2.8 mm Hg/μL vs. 8.2 ± 2.6 mm Hg/μL, p = .01, respectively), with recovery of E[sub max] by 45 min in control hearts only. We conclude that exposure of hearts to isoproterenol during warm cardioplegic arrest has a deleterious effect that may be mediated through mechanisms independent of increased myocardial oxygen consumption. [ABSTRACT FROM AUTHOR]