Scandinavian cardiovascular journal. Supplement最新文献

1. Low pH and lactic acid perfusion evoke a reproducible, and concentration-dependent outflow of CGRP from the isolated heart. 2. PGI2 causes outflow of CGRP from the isolated heart. Furthermore, low pH perfusion causes release of PGI2, and cyclo-oxygenase inhibition attenuates not only this release of PGI2, but also the outflow of CGRP that is evoked by low pH perfusion, indicating that a portion of the C-fibre activation exerted by low pH is mediated by PGI2. 3. The outflow of CGRP that is caused by low pH but not that evoked by capsaicin or PGI2 is dependent on the endothelium, whereas the vasodilating effect of CGRP is preserved after removal of the endothelium. 4. TTX attenuates release of CGRP caused by low concentrations of capsaicin, indicating that an axon reflex mechanism in the peripheral endings of C-fibre afferents can augment local outflow of CGRP. 5. Outflow of CGRP evoked by low pH and capsaicin have common features, such as sensitivity to RR and CPZ. N-type calcium channels are involved in release of CGRP by both stimuli. 6. In the coronary vasculature, exogenous CGRP augmented post-occlusive hyperaemia. 7. In the pig in vivo, CGRP causes marked dose-dependent reduction of systemic vascular resistance. This effect of CGRP was partly reduced by CGRP(8-37). 8. Capsaicin pretreatment resulted in lower myocardial levels of CGRP, and ischaemic myocardium had lower content of CGRP than non-ischaemic areas. Capsaicin-treated animals had larger myocardial infarctions, possibly due to depletion of CGRP. When endogenous stores of CGRP were intact, administration of additional CGRP to the ischaemic myocardium had no cardioprotective effect. 9. In patients undergoing CABG without CPB, 10-20 minutes of local ischaemia (as evidenced by a net production of lactate) was associated with increased levels of CGRP in coronary sinus blood. 10. Based on the present findings it may therefore be suggested that local cardiac CGRP-release from capsaicin-sensitive C-fibre afferents during myocardial ischaemia functions as an endogenous physiological protective response. The possibility thus exists that effects of CGRP observed in animal studies may play a role in human myocardial ischaemia.

Coronary artery diseases (CAD) are main causes of morbidity and hospitalisation in western countries and CAD patients are at considerable risk of suffering further cardiac events. The development and evaluation of secondary prevention programmes therefore an important task. This thesis includes investigations on CAD patients admitted to a secondary prevention programme at Malmö University Hospital, Malmö, Sweden. Four weeks after discharge from the hospital, consecutive male and female patients aged 50-70 years with acute myocardial infarction (AMI) or treated with coronary artery bypass grafting (CABG) surgery were randomised to a hospital organised preventive intervention or to usual follow-up at their general practitioners. In the three studies using this randomised design, 87 (study II), 90 (study IV), and 106 (study V) intervention patients were available for evaluation. In addition, without randomisation, lipid levels at four weeks after the event was compared with levels estimated within 24 hours after onset of symptoms in 141 AMI patients (study I), and quality of life (QL) were estimated by questionnaire at one month and at one year after the event in 266 AMI, 94 CABG, and 16 percutaneous transluminal coronary angioplasty (PTCA) patients (study III). The prevention programme was effective in improving food habits but showed no impact on smoking habits or physical exercise in AMI patients (study II). The intervention also did not show any significant improvement in working capacity in AMI and CABG patients. However, working capacity improved in both intervention and reference CABG patients, most probably due to improved coronary circulation from the surgery (study IV). Cholesterol levels decreased significantly in AMI and CABG intervention patients as compared to the corresponding reference patients. This difference most likely was due to a higher frequency of lipid lowering drugs used in the intervention patients (study V). The prevention programme also decreased body mass index significantly in AMI but not in CABG patients (study V). In AMI patients receiving thrombolysis, cholesterol levels estimated within 24 hours after onset of symptoms and at four weeks after the event were virtually equal. In AMI patients not receiving thrombolysis, the lipid estimates from four weeks after the event were slightly, but significantly, above the within 24 hours from onset of symptoms estimates (study I). One month after the event, both somatic and psychological aspects of QL were negatively affected in AMI and CABG patients compared to population controls. One year after the event, patients differed from controls mainly in somatic symptoms (study III). Thus, the intervention programme was most successful in affecting lipid levels and food habits in AMI patients. QL was considerably affected in patients following an cardiac event, especially during the initial recovery phase. In addition, in patients receiving thrombolysis, cholesterol levels e

In summary, carvedilol lowers blood pressure effectively. There is a decrease in left ventricular mass. Carvedilol has a good metabolic profile and seems to improve insulin sensitivity. Through its effects on the endothelial function and its antioxidative properties carvedilol has positive effects on the atherosclerotic process. Carvedilol also decreases microalbuminuria. In several aspects carvedilol differs from the conventional beta-blocking drugs, and some of these effects are now being investigated in new studies.

1. The experimental model using periods of ventilation with a gas mixture containing 10% oxygen in the anesthetized pig was found to induce HPV that was reproducible and remained stable for up to two hours. 2. Intrapulmonary infusion of ET-1 during normoxia resulted in a dose-dependent increase in the SVR with a concomitant decrease in CO and rise in PVR. Infusion of ET-3 and S6c evoked similar responses, but of a considerably smaller magnitude. The dose-dependent systemic vasoconstriction evoked by ET-1 infusion was reduced after administration of the combined ETA and ETB receptor antagonist bosentan as well as the selective ETA receptor blockers BMS-182874 and TBC-11251 indicating that this effect is primarily mediated by ETA receptors. ETA receptors are present in porcine pulmonary arteries, since BMS-182874 caused a rightward shift of the concentration-response curve to ET-1 in vitro. 3. Administration of selective ETA- or combined ETA and ETB antagonists but not of a selective ETB antagonist reduced the SVR in normoxic pigs, indicating that ET acting through ETA receptors contributes to systemic vascular tone in the pig. In addition, ETA selective and non-selective ETA and ETB antagonists produced a reduction of PVR, although this effect was less consistent than the influence on SVR. This indicates that ETA receptors may contribute to basal pulmonary vascular tone. The plasma levels of ET-1 increased following the non-selective ET receptor antagonist bosentan but were unaffected by selective ETA receptor antagonism. 4. Intrapulmonary infusion of ET-1 produced in low doses a pulmonary vasodilatation during HPV in the pig. This pulmonary vasodilatory effect was also evident when ET-3 or S6c was infused. The pulmonary vasodilatory effect of ET-1 infusion was abolished following administration of the selective ETB receptor antagonist BQ-788, indicating that the pulmonary vasodilatory effect of ET in HPV in the pig is mediated by ETB receptors. Higher doses of ET-1 infusion during HPV resulted in systemic and pulmonary vasoconstriction. 5. Both combined ETA and ETB blockade using bosentan and selective ETA receptor inhibition using BMS-182874 or TBC-11251 reduced the development of HPV in the pig. In addition, bolus injection of TBC-11251 reversed already established HPV. Selective ETB receptor antagonism had no effect on HPV. These findings suggest that ETA receptor activation contributes to HPV in the pig. 6. The concentration-dependent contraction evoked by ET-1 in human vessels in vitro (LAD, IMA, PA, SV) was reduced after incubation with BQ-123 and bosentan. Inhibition of NO- and prostaglandin-synthesis enhanced the contractions in the LAD and IMA, but not in the PA and SV. These findings are in concord with a predominance of ETA receptors in the investigated vessels. Nitric oxide and prostacyclin seem to be important determinants of the functional response to ET in human LAD and IMA, but of less importance in the PA and SV. 7. In the