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Abstract: Background: Atrial fibrillation (AF) is associated with extracellular matrix remodeling involving atrial fibrosis and atrial dilatation. Angiotensin II mediated pathways and matrix metalloproteinases (MMPs) have been implicated in these processes. Our aim was to study atrial structural remodeling and the expression of the angiotensin receptor subtypes and MMPs and their inhibitors (TIMPs) in patients with mitral valve disease with and without AF. Methods and results: Biopsies from right and left atrial appendages (RA and LA) were taken from patients undergoing CABG (n =9, all in sinus rhythm (SR)) or mitral valve surgery (MVS; n =19; 9 with permanent AF and 10 in SR). Patients with MVS and AF had significantly larger atria (versus MVS and SR: p =0.02; versus CABG: p <0.01). The MVS patients had significantly more fibrosis than the control CABG group. Fibrosis was increased in both the AF and SR MVS groups in the LA, but only in the MVS–AF group in the RA. These AF patients had significantly more tricuspid regurgitation than SR patients. MMP-1 was down-regulated in LA of MVS patients (p =0.02) independent of the underlying rhythm (SR or AF; p =0.95). In RA biopsies, MMP-1 was down-regulated only in the MVS and AF group. MMP-9 was down-regulated in the MVS patients compared to CABG both in the RA and LA, and without a difference between the SR and AF groups. Protein expression of AT-1, AT-2, MMP-2, TIMP-1, -2 and -4, TNF-α, and TNF-α-converting enzyme did not differ significantly between the 3 groups. Conclusions: Concordant changes between MMP-expression and fibrosis during mitral valve disease, both in LA and RA, suggest involvement of MMPs in structural atrial remodeling. AF itself did not contribute to altered fibrosis or MMP-expression in the LA. The association between AF and RA changes may be precipitated by greater hemodynamic load due to tricuspid regurgitation in these patients. [Copyright &y& Elsevier]

Objective: Ischemic preconditioning (IP) describes the adaptation of the myocardium to ischemic stress preceded by short periods of ischemia and reperfusion. However, its cardioprotective mechanisms are not completely understood. We assessed the effect of IP on ventricular energetics in an in-vivo sheep model. Methods: IP was performed in six sheep by three 5 min aortic cross-clamping periods interspersed with 5 min of reperfusion during cardiopulmonary bypass and with six sheep as time-matched controls. Global myocardial ischemia was subsequently achieved by 30 min aortic cross-clamping with left ventricular unloading during normothermic cardiopulmonary bypass. Weaning from cardiopulmonary bypass was performed 40 min after reperfusion. At baseline, after treatment (IP or time-matched cardiopulmonary bypass), and up to 100 min after reperfusion, left ventricular pressure–volume loops were measured using a conductance catheter during a right heart bypass preparation. Contractility, diastolic function, and ventriculo–arterial coupling were evaluated. Ventricular energetics [the relation between myocardial oxygen consumption (MVO2) and systolic pressure–volume area (PVA)] was also evaluated. A right heart bypass was instituted to control the preload and to decompress the right ventricle completely, thereby eliminating parallel conductance variation and minimizing the contribution of the right ventricle to MVO2. Results: IP reduced unloaded MVO2 (PVA-independent MVO2). Contractility, diastolic function, and ventriculo–arterial coupling in the IP group were better preserved than in the control group after ischemia-reperfusion. Conclusions: IP reduces unloaded MVO2, and preserves contractility, diastolic function, and ventriculo–arterial coupling after 30 min global myocardial ischemia in an in-vivo sheep model. [Copyright &y& Elsevier]

Objective: Brain death induces important haemodynamic changes in rats, with a drop in arterial blood pressure, left ventricular developed pressure and dP/dtmax to less than 50% of its control value. Myocardial damage was reported to contribute to this paradigm. The role of potential underlying pathogenetic mechanisms, such as a circulating cardiodepressant factor, NO, endogenous opioid peptides, vagal or β-adrenergic activation, or hypophyseal dysfunction, were explored, but none of them could be demonstrated as the culprit. This study investigated whether functionally important intrinsic myocardial damage was induced by brain death in the rat, and whether coronary endothelial cell dysfunction, possibly causing multifocal ischaemia, contributed to this. Methods: Brain death was induced in rats by sudden inflation of an intracranial balloon. Extensive haemodynamic measurements, including heart rate, arterial blood pressure, central venous pressure, left ventricular pressure, and cardiac output, were performed. Hearts excised 1 and 4 h after brain death were examined histologically. The contractile reserve of these hearts was tested by administration of increasing doses of adrenaline (10−9 to 10−6 mol/l) in a Langendorff system. The coronary endothelium was tested with regard to its barrier function for macromolecules by determining the extravasation of injected Evans blue, and with regard to its vasoactive function by testing the effects of serotonin and nitroglycerin in a Langendorff system. Results: The haemodynamic measurements suggested that the cardiovascular collapse consisted mainly in alterations in afterload. Contractile reserve, as tested with increasing adrenaline doses, revealed a normal dose–response curve. No histological myocardial damage was found after brain death in rats. No abnormal extravasation of Evans blue was seen. Coronary vasoreactivity towards nitroglycerin and serotonin was normal. Conclusion: Myocardial damage, if present at all, contributes only minimally to the changes in haemodynamic profile seen after brain death in the rat, and the coronary endothelium appears to preserve its barrier and vasoactive function. [ABSTRACT FROM PUBLISHER]

Objective: Brain death-induced haemodynamic collapse in rats is not caused by intrinsic myocardial damage as shown in the accompanying paper. We investigated whether this collapse could be caused by the withdrawal of the basal adrenergic tone. Methods: Heart rate and blood pressure variability was studied in rats before and after brain death. The effect of high doses of phentolamine, propranolol or their combination administered before or after brain death was assessed. Results: Heart rate variability in the respiratory frequency range significantly increased, whereas in the low-frequency range it tended to decrease after brain death. Systolic and diastolic blood pressure variability up to 0.18 Hz largely disappeared, but stayed unchanged in the respiratory frequency range. High-dose combined phentolamine and propranolol pretreatment induced a haemodynamic picture comparable to the situation seen after brain death without pharmacological intervention. Brain death did not further deteriorate the haemodynamic situation after combined pretreatment. On the other hand, once the haemodynamic collapse after brain death had settled, adrenergic blockade had no important influence any more. Conclusion: We conclude that the haemodynamic situation seen after brain death is one of profound sympathetic withdrawal. [ABSTRACT FROM PUBLISHER]