BackgroundMesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status.ObjectivesTo examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance.MethodsHealthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups.ResultsCFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted.ConclusionOverall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.

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IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

Neurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear. Objective: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures. Methods: We studied 28 patients (50% male, mean age 41 ± 14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included nine tilt sessions (three times a week, 30 min) (60 • ---6 sessions, 70 • ---3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10 • head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24 ± 12 months). Results: Over the course of the TT program there was a significant increase in total peripheral resistance (1485 ± 225 vs. 1591 ± 187 dyn s cm −5 , p < 0.05), with a decrease in standard deviation (206 ± 60 vs. 150 ± 42, p < 0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0 ± 3.2/patient in the 12 months before TT vs. 1.4 ± 0.8/patient post-TT, p < 0.05). Conclusion:In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance. PALAVRAS-CHAVE