The optimisation of the aqueous solubility of organic carbon monoxide releasing molecules based on a norborn-2-en-7-one scaffold is reported. This culminated in the synthesis of oCOm-54 and oCOm-56 which contain water solubilising polyethylene oxide groups. Both compounds are highly water soluble and release CO at pH 7.4 with half-lives of 180 and 320 minutes respectively, to produce a reversible vasodilatory response in isolated, preconstricted tissue. Preliminary analysis indicates these oCOms are capable of forming micellar particles. Both oCOms exhibit significantly less cellular toxicity in AC16 human cardiomyocytes than earlier amine-containing oCOms.

Attenuation of seizure with diazepam offered no cardiac protection; however, coadministration of atenolol with diazepam prevented the development of seizure-induced cardiac dysfunction. This study demonstrates that atenolol intervention should be strongly considered as an adjunct clinical treatment to reduce cardiomyopathy during seizures.

Cardiorenal syndrome, de novo renal pathology arising secondary to cardiac insufficiency, is clinically recognised but poorly characterised. This study establishes and characterises a valid model representative of Type 2 cardiorenal syndrome. Extensive permanent left ventricular infarction, induced by ligation of the left anterior descending coronary artery in Lewis rats, was confirmed by plasma cardiac troponin I, histology and cardiac haemodynamics. Renal function and morphology was assessed 90-days post-ligation when heart failure had developed. The involvement of the paraventricular nucleus was investigated using markers of inflammation, apoptosis, reactive oxygen species and of angiotensin II involvement. An extensive left ventricular infarct was confirmed following coronary artery ligation, resulting in increased left ventricular weight and compromised left ventricular diastolic function and developed pressure. Glomerular filtration was significantly decreased, fractional excretion of sodium and caspase activities were increased and basement membrane thickening, indicating glomerulosclerosis, was evident. Interestingly, angiotensin II receptor I expression and reactive oxygen species levels in the hypothalamic paraventricular nucleus remained significantly increased at 90-days post-coronary artery ligation, suggesting that these hypothalamic changes may represent a novel, valuable pharmacological target. This model provides conclusive morphological, biochemical and functional evidence of renal injury consequent to heart failure, truly representative of Type-2 cardiorenal syndrome.Cardiorenal syndrome (CRS) is a clinically recognised but poorly characterised condition which is generally divided into multiple subtypes to aid the selection of specialised interventions 1 . Type-2 CRS describes chronic cardiac dysfunction, such as chronic heart failure (CHF), leading to progressive chronic kidney disease (CKD). This worsening renal function can then accelerate the underlying myocardial dysfunction. Chronic kidney failure has been reported in 68.3% of heart failure (HF) patients, with reduced creatinine clearance (CrCl) 2 and decreased estimated glomerular filtration rate (eGFR) 3 being recognised predictive factors for mortality. Conversely, improved renal function promotes a favourable prognosis in HF 4 .Current international clinical guidelines direct that CKD should be viewed as a prevalent condition of varying severity, and press the need for early detection and improved clinical management 5 . Pathological processes implicated in the generation of CKD secondary to HF include: haemodynamic parameters, excessive autonomic nervous system (ANS) efferent output, systemic release of endocrine mediators and proinflammatory cytokines, impairment of endogenous vasodilatory mechanisms, erythropoietin imbalances and anaemia 6-12 . Activation of systemic and renal renin-angiotensin aldosterone system (RAAS) results in increased angiotensin II (AngII) and aldosterone mediated effects on renal electrolyte and water reten...

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