There is increasing evidence that cyclooxygenase (COX)-2 possess both angiogenic and cardioprotective properties. We examined the effects of hypoxic cardiac myocytes (H9c2 cells) on COX-2 expression in human umbilical vein endothelial cells (HUVECs) to determine the pathway involved in COX-2 regulation. The medium from hypoxic (<1% O2) cardiac myocytes (HMCM) or normoxic cardiac myocytes (21% O2) was added to HUVEC cultures. HMCM induced a transient increase of COX-2 mRNA expression at 1 and 3 h without affecting the COX-1 mRNA level. A similar effect also observed in HMCM from cultured primary cardiac myocytes (rat neonatal cardiac myocytes). The increased COX-2 mRNA was associated with a time-dependent increase in COX-2 protein expression. COX-2 was significantly induced by VEGF (4.86 ± 1.03-fold) and IL-1β (3.93 ± 0.89-fold) and slightly increased by TNF-α but not by FGF2, IGF-1, or PDGFs. Analysis of proteins secreted in HMCM showed increased levels of VEGF but not IL-1β or TNF-α. The HMCM-induced COX-2 expression was inhibited by the addition of an anti-VEGF neutralizing antibody. VEGF induced endothelial cell COX-2 expression by both increasing COX-2 transcription and prolonging the COX-2 mRNA half-life. Furthermore, staurosporine, a nonselective PKC inhibitor, prevented the induction of VEGF by hypoxia. Both a selective PKC-α and -β inhibitor and an inducible nitric oxide synthase (NOS) inhibitor decreased the induction of COX-2 by HMCM and VEGF. Finally, HMCM-induced upregulation of COX-2 was accompanied by upregulation of PGI2 and PGE2. These results suggest that VEGF is one of the principal factors produced by hypoxic myocytes that is responsible for the induction of endothelial cell COX-2 expression. This process likely involves both PKC and NOS pathways. Our findings have important implications regarding the cardiac protection of COX-2 in ischemic heart disease.

We observed that excess circulating inflammation markers, being characteristic of unstable coronary artery disease, are released from noncoronary sources. Thus, it may be speculated that systemic inflammation precedes local inflammation at the plaques, thereby transforming coronary disease from a stable to an unstable form.

BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is a novel early marker of acute kidney injury for which has been shown that it can also be released from the injured myocardium. Our aim was to correlate urine NGAL with markers of in-hospital heart failure in patients with acute ST-elevation myocardial infarction (STEMI).MethodsWe prospectively included 61 consecutive STEMI patients after primary percutaneous coronary intervention and estimated admission and in-hospital urine NGAL, serum creatinine, troponin I, leucocytes, CRP, N-terminal pro brain natriuretic peptide (NT-proBNP) levels and ejection fraction by echocardiography. Urine NGAL levels were compared between patients with and without HF defined as serum NT-proBNP > 400 pmol/l and were correlated to markers of heart failure, inflammations and of kidney function.ResultsUrine NGAL levels and CRP was significantly higher in participants with heart failure compared to those with NT-proBNP below 400 pmol/l. Urine NGAL level of 50 ng/ml had 90 % specificity for HF, the sensitivity was low at 25 %. Comparison of participants with NGAL levels < 50 ng/ml and ≥ 50 ng/ml at admission and after 12 h revealed a significant difference in NT-proBNP levels, left ventricle ejection fraction, markers of inflammation and of kidney function. Urine NGAL level was independently associated with NT-proBNP level.ConclusionsThe level of urine NGAL early after myocardial infarction is associated with NT-proBNP concentration and even NGAL levels below 137 ng/ml, the usually reported normal cut-off value, had high specificity for HF in our sample.

AbstractIn treatment of manic-depressive conditions long-term lithium therapy may be combined with an effective and relatively safe antidepressant venlafaxine. Combined overdose may increase the risk of early toxicity of both drugs and of delayed lithium intoxication, responding to symptomatic and renal replacement therapy. We present a patient with combined lithium and venlafaxine self-poisoning with nothing but delayed signs of lithium intoxication with the emphasis on early and late treatment. 41-year old woman attempted suicide by large amount of lithium and venlafaxine. On admission she was asymptomatic, but with increased serum lithium over 5mmol/L. After gastric lavage, active charcoal and laxative administration she was receiving IV fluids. After a delay of 63 hours she deteriorated acutely by disorientation, confusion, fasciculation and tremor and was readmitted to Intensive care unit. In spite serum lithium decreased to 2mmol/L clinical signs were attributed to delayed lithium intoxication. After symptomatic and renal replacement therapy the patient’s condition improved after few days. We conclude that decontamination procedures are effective in particular for venlafaxine poisoning. If increased serum lithium levels are noted renal replacement therapy may be started even in asymptomatic patients as delayed lithium intoxication is most likely after few days.