Are early clinical effects of cholesterol lowering mediated through effects on inflammation?

In a randomized, double-blind trial in 3086 patients with unstable angina pectoris or non-Q wave myocardial infarction we investigated if 80 mg of atorvastatin daily could improve outcome of cardiovascular events during a short period of time (16 weeks) compared with placebo. Baseline LDL cholesterol was 3.2 mmol L-1 (124 mg dL-1) and decreased by 40% to 1.9 mmol L-1 (72 mg dL-1) during atorvastatin treatment. The primary endpoint, which was a composite of death, non-fatal acute myocardial infarction, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischaemia with objective evidence and requiring emergency rehospitalization occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group. The relative risk was 0.84 and 95% confidence interval was 0.70-1.00 (P = 0.048). Thus for patients with acute coronary syndromes, lipid-lowering therapy with high dose atorvastatin reduces recurrent ischaemic events in the short-term. A possible mechanism behind this rapid clinical effect induced by statin treatment is on inflammatory processes. Recent studies strongly suggest that acute T-cell activation is involved in the pathogenesis of unstable angina. In another study we investigated whether circulating T cells showed signs of activation in patients with stable angina pectoris (SA). Systemic venous blood samples were taken from 38 men with SA and 42 healthy controls. The T-cell receptor expression was assessed by three-colour flow cytometry using monoclonal antibodies against CD3,CD4, CD8, CD25 and human leucocyte antigen (HLA)-DR. Soluble interleukin-2 receptor (sIL-2R) was measured as the circulating form in serum. Levels of circulating CD3+ and CD4+ T cells tended to be higher in patients compared with controls. Patients were also shown to have a significant increase in CD4+ T cells expressing the activation markers CD25 (P < 0.05) and HLA-DR (P < 0.01). Furthermore, serum levels of sIL-2R were significantly higher (P < 0.001) in patients than in controls. We also observed that the T-cell response was more pronounced in patients without simvastatin treatment (n = 18) compared with simvastatin-treated patients (n = 20). In conclusion, our findings indicate that a continuous immune system activation takes place in patients with chronic angina pectoris, predominantly involving proliferation of CD4+ T cells. Statin treatment seems to be able to decrease this inflammatory response.

Differential effect on vasodilatation and pain after intradermal capsaicin in humans during decay of intravenous regional anesthesia with mepivacaine.

BACKGROUND AND OBJECTIVES: When given intracutaneously, capsaicin can cause burning pain by central propagation in thin afferents, as well as neurogenic vasodilatation, reflecting antidromic conduction in the same fibers. We wanted to test the hypothesis that an intravenous regional block (IVRA) inhibits these two phenomena to a similar degree. METHODS: Sixteen healthy volunteers participated. A bilateral IVRA was performed by simultaneously injecting mepivacaine in one arm and normal saline in the other in a randomized, double-blind manner. Ten minutes after release of the tourniquet, neurogenic inflammation was inflicted in each forearm by intracutaneous capsaicin. Microvascular skin blood flow was measured with a laser Doppler perfusion imager. The area of the flare and the flow therein were measured, taking into account the change in baseline caused by mepivacaine treatment and the postischemic hyperemia. Pain was repeatedly evaluated by visual analog scale. RESULTS: The reactive hyperemia following arterial occlusion was less in the mepivacaine-treated arm 10 minutes after tourniquet release (P=.026). Intracutaneous capsaicin elicited a flare in both arms. The area of the flare was smaller 10 minutes after capsaicin (P=.009) in the mepivacaine-treated arm. There was no difference between the arms concerning the mean blood flow within the flare or in ischemic or capsaicin-induced pain. CONCLUSIONS: Mepivacaine, given as an IVRA, had no effect on the post-IVRA sensory function of thin afferents but differentially decreased the spread of the capsaicin-induced flare.