1 We evaluated the role of SH-groups in improvement of endothelial dysfunction with ACEinhibitors in experimental heart failure. To this end, we compared the vasoprotective e ect of chronic treatment with zofenopril (plus SH-group) versus lisinopril (no SH-group), or Nacetylcysteine (only SH-group) in myocardial infarcted (MI) heart failure rats. 2 After 11 weeks of treatment, aortas were obtained and studied as ring preparations for endothelium-dependent and -independent dilatation in continuous presence of indomethacin to avoid interference of vasoactive prostanoids, and the selective presence of the NOS-inhibitor L-NMMA to determine NO-contribution. 3 Total dilatation after receptor-dependent stimulation with acetylcholine (ACh) was attenuated (749%, P50.05) in untreated MI (n=11), compared to control rats with no-MI (n=8). This was in part due to impaired NO-contribution in MI (750%, P50.05 versus no-MI). At the same time the capacity for generation of biologically active NO after receptor-independent stimulation with A23187 remained intact. 4 Chronic treatment with n-acetylcysteine (n=8) selectively restored NO-contribution in total dilatation to ACh. In contrast, both ACE-inhibitors fully normalized total dilatation to ACh, including the part mediated by NO (no signi®cant di erences between zofenopril (n=10) and lisinopril (n=8)). 5 Zofenopril, but not lisinopril, additionally potentiated the e ect of endogenous NO after A23187-induced release from the endothelium (+100%) as well as that of exogenous NO provided by nitroglycerin (+22%) and sodium nitrite (+36%) (for all P50.05 versus no-MI). 6 We conclude that ACE-inhibition with a SH-group has a potential advantage in improvement of endothelial dysfunction through increased activity of NO after release from the endothelium into the vessel wall. Furthermore, this is the ®rst study demonstrating the selective normalizing e ect of Nactylcysteine on NO-contribution to ACh-induced dilatation in experimental heart failure.

At present, there is no reliable antianginal drug therapy for patients with cardiac syndrome X. Therefore, the effect of electrical neuromodulation on refractory angina pectoris and myocardial perfusion in cardiac syndrome X was assessed. Eight patients (aged 55+/-7 years) with heterogeneous myocardial perfusion and no esophageal abnormalities were included. The subjects were nonresponders to antianginal drug therapy. Angina pectoris attacks and myocardial perfusion dynamics were evaluated by positron emission tomography at baseline and following 4 weeks of (transcutaneous electrical nerve stimulation) TENS. Following TENS there was a reduction of angina pectoris episodes (baseline 20+/-3, TENS 3+/-1; p=0.012), and short acting nitroglycerin intake per week (baseline 10+/-3, TENS 2+/-1; p=0.008). The rate pressure product (mmHg min(-1)) during the cold pressor test (CPT) was reduced during TENS (baseline 12800+/-1200, TENS 11500+/-900; p=0.02). Following TENS, the perfusion reserve ratio between rest and dipyridamole flow increased (baseline 1.59+/-0.15, TENS 1.90+/-0.11 ml min(-1)x 100g; p=0.05). The coronary vascular resistance had a trend towards a reduction (baseline 0.96+/-0.04, TENS 0.85+/-0.06 mmHg min(-1)x 100 g/ml; p=0.06) during CPT. This observation may suggest that neurostimulation improves angina pectoris with a concomitant improvement of myocardial perfusion in cardiac syndrome X.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. VEGF gene therapy improves perfusion of ischemic myocardium in experimental models and possibly in patients with end-stage coronary artery disease. In addition to its proliferative and migratory effect on endothelial cells, it also activates and up-regulates endothelial nitric oxide synthase (eNOS). Therefore, the authors investigated coronary endothelium-dependent vasodilatation in patients before and after VEGF gene therapy. The effect of intracoronary acetylcholine infusion on coronary diameter was assessed at baseline and after 3 months follow-up in patients with end-stage coronary artery disease treated with VEGF gene and in controls scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) (acetylcholine test at diagnostic angiography and before a subsequently scheduled PTCA). Five out of six VEGF patients experienced a reduction in anginal complaints. Angiographic evidence for improved collateral filling was evident in two out of six patients. The vasoconstrictive response to acetylcholine was partly converted into dilatation. In contrast, the acetylcholine response in control patients remained vasoconstrictive. In conclusion, VEGF gene therapy has an important beneficial effect on the functional characteristics of the myocardial vascular network. Therefore, this therapy can potentially play an important role in all stages of the atherosclerotic process.

Background. Little is known about the diagnostic accuracy of global LV function assessment by electromechanical endocardial mapping (EEM). The aim of the present study was to determine the relationship between global left ventricular (LV) function measured by EEM and biplane left ventricular contrast angiography (LVA) after ST-elevation myocardial infarction (STEMI).Methods. Thirty-seven patients underwent LVA and EEM during routine coronary angiography four months after primary percutaneous intervention for STEMI. Global LV function parameters were available from both techniques in all patients. LVA was regarded as reference standard.Results. All procedures were carried out without adverse events. Average age was 55+/-10 years and 84% were male. EEM showed an overestimation of end-diastolic volume (EDV) and end-systolic volume (ESV) of 6.5 ml and 25.5 ml, respectively. Correlation (r) was 0.84 (p<0.001) for EDV and 0.74 (p<0.001) for ESV. Average left ventricular ejection fraction (LVEF) measured by EEM was 17.2% point (+/-11.3% point) lower compared with LVA (r=0.69, p<0.001).Conclusion. Although global functional parameters by EEM correlated well with LVA, the relatively large differences in terms of absolute values for ventricular volumes and LVEF render the two techniques non-interchangeable for global LV-function-data. (Neth Heart J 2010;18:72-77.).