Background In patients with ST-segment elevation myocardial infarction (STEMI), the importance of a well-balanced inflammatory reaction has been recognized for years. Monocytes play essential roles ...in regulating inflammation. Hence, we investigated the association between inflammatory characteristics of monocytes and myocardial injury and functional outcome in patients with STEMI. Methods Using flow cytometry, the levels of classical (CD14++ CD62L+ ) and nonclassical (CD14+ CD62L− ) monocytes were analyzed in peripheral blood in 58 patients with STEMI at a median of 5 days (4-6 days) after primary percutaneous coronary intervention. In addition, the monocytic expression of several surface molecules and formation of monocyte-platelet complexes were measured. All patients underwent cardiovascular magnetic resonance imaging at baseline and 4-month follow-up. Results At baseline, patients with high levels of classical monocytes had impaired left ventricular (LV) ejection fraction ( P = .002), larger infarct size ( P = .001), and, often, presence of microvascular obstruction ( P = .003). At follow-up, high levels of classical monocytes were negatively associated with the regional systolic LV function independent of the transmural extent of infarction. In contrast, positive associations for the levels of nonclassical monocytes were observed. Finally, up-regulation of macrophage 1 by blood monocytes and increased formation of monocyte-platelet complexes were associated with enhanced myocardial injury at baseline and impaired LV function at follow-up. Conclusions This study shows an association between a proinflammatory monocyte response, characterized by high levels of classical monocytes, and severe myocardial injury and poor functional outcome after STEMI. Future studies are required to investigate the biologic nature of this association and therapeutic implications.
Objective: Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and a target for pharmacological and catheter-based therapies. The effect of a physiological ...sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown. Design and method: We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, resting, and hyperemia following intrarenal dopamine (30 ug/kg). Changes in perfusion pressure were expressed as delta mean arterial pressure, changes in flow velocity as percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model. Results: We included 18 patients with median age 57 years (range 27–85), 61% male in the final analysis. An overview of the hemodynamic responses is given in Figure 1. During static handgrip mean renal arterial pressure increased by 15.2 mmHg (range 4.2–53.0), while flow decreased by 11.2%, but with large variation between individuals (range -13.4–49.8%). Intraglomerular pressure increased with 4.2 mmHg (range -3.9–22.1). Flow velocity under resting conditions remained stable with median 100.6% (range 82.3–114.6) compared to baseline. During hyperemia, maximal flow was 180% (range 111–281), while intraglomerular pressure decreased to 33.0 mmHg IQR 26.7–39.8. Changes in renal pressure and flow during handgrip exercise were correlated (rho = -0.68; p = 0.002). Conclusions: We show that there are significant variations in the response to sympathetic stimulation following static handgrip exercise using invasive renal arterial measurements. These results demonstrate that intra-arterial renal hemodynamic measurements can be used to determine the renal effect of systemic sympathetic stimulus and allows identification of patients with higher and lower sympathetic control of renal perfusion. This may be useful in determining the response to therapeutic interventions aimed at altering renal sympathetic control.
Objectives In the present substudy of the Hebe trial, we investigated the effect of intracoronary bone marrow mononuclear cell (BMMC) and peripheral blood mononuclear cell (PBMC) therapy on the ...recovery of microcirculation in patients with reperfused ST-segment elevation myocardial infarction (STEMI). Background Several studies have suggested that cell therapy enhances neovascularization after STEMI. Methods Paired Doppler flow measurements were available for 23 patients in the BMMC group, 18 in the PBMC group, and 19 in the control group. Coronary flow was assessed at 3 to 8 days after primary percutaneous coronary intervention (PCI) and repeated at 4-month follow-up, with intracoronary Doppler flow measurements. Results At baseline, the coronary flow velocity reserve was reduced in the infarct-related artery and improved over 4 months in all 3 groups. The increase of coronary flow velocity reserve did not significantly differ between the 2 treatment groups and the control group (BMMC group: 2.0 ± 0.5 to 3.1 ± 0.7; PBMC group: 2.2 ± 0.6 to 3.2 ± 0.8; control group: 2.0 ± 0.5 to 3.4 ± 0.9). Additionally, the decrease in hyperemic microvascular resistance index from baseline to 4-month follow-up was not statistically different between the 2 treatment groups and the control group. Conclusions In STEMI patients treated with primary PCI in the Hebe trial, adjuvant therapy with BMMCs or PBMCs does not improve the recovery of microcirculation. Therefore, our data do not support the hypothesis of enhanced neovascularization after this mode of cell therapy. (Multicenter, randomised trial of intracoronary infusion of autologous mononuclear bone marrow cells or peripheral mononuclear blood cells after primary percutaneous coronary intervention PCI; ISRCTN95796863 )
PDF
