In our lipopolysaccharide model, with resuscitation targeted at blood pressure, contrast-enhanced ultrasound imaging can identify renal microvascular alterations by showing prolonged contrast enhancement in microcirculation during shock, worsened by resuscitation with fluids. Concomitant analysis of sublingual microcirculation mirrored those observed in the renal microcirculation.

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Key points Although optogenetics has clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies lack the capability to react acutely to ongoing cardiac wave dynamics.Here, we developed an all‐optical platform to monitor and control electrical activity in real‐time.The methodology was applied to restore normal electrical activity after atrioventricular block and to manipulate the intraventricular propagation of the electrical wavefront.The closed‐loop approach was also applied to simulate a re‐entrant circuit across the ventricle.The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time all‐optical stimulation can control cardiac rhythm in normal and abnormal conditions. AbstractOptogenetics has provided new insights in cardiovascular research, leading to new methods for cardiac pacing, resynchronization therapy and cardioversion. Although these interventions have clearly demonstrated the feasibility of cardiac manipulation, current optical stimulation strategies do not take into account cardiac wave dynamics in real time. Here, we developed an all‐optical platform complemented by integrated, newly developed software to monitor and control electrical activity in intact mouse hearts. The system combined a wide‐field mesoscope with a digital projector for optogenetic activation. Cardiac functionality could be manipulated either in free‐run mode with submillisecond temporal resolution or in a closed‐loop fashion: a tailored hardware and software platform allowed real‐time intervention capable of reacting within 2 ms. The methodology was applied to restore normal electrical activity after atrioventricular block, by triggering the ventricle in response to optically mapped atrial activity with appropriate timing. Real‐time intraventricular manipulation of the propagating electrical wavefront was also demonstrated, opening the prospect for real‐time resynchronization therapy and cardiac defibrillation. Furthermore, the closed‐loop approach was applied to simulate a re‐entrant circuit across the ventricle demonstrating the capability of our system to manipulate heart conduction with high versatility even in arrhythmogenic conditions. The development of this innovative optical methodology provides the first proof‐of‐concept that a real‐time optically based stimulation can control cardiac rhythm in normal and abnormal conditions, promising a new approach for the investigation of the (patho)physiology of the heart.

The action potential of Purkinje fibres is markedly shortened by tetrodotoxin, suggesting the possibility that a slowly inactivating sodium current might flow during the plateau. The aim of the present experiments was to investigate, in canine cardiac Purkinje single cells by means of a whole cell patch clamp technique, whether a sodium current slowly inactivates at less negative potentials and (if so) some of its distinctive characteristics. The results showed that a 500 ms depolarizing step from a holding potential of −90 mV to −50 mV induced the fast inward current I Na (labelled here I Na1 ). With steps to −40 mV or less negative values, a slowly decaying component (tentatively labelled here I Na2 ) appeared, which peaked at −30 to −20 mV and decayed slowly and incompletely during the 500 ms steps. The I Na2 was present also during steps to −10 mV, but then the transient outward current (I to ) appeared. When the holding potential (V h ) was decreased to −60 to −50 mV, I Na2 disappeared even if a small I Na1 might still be present. Tetrodotoxin (30 µM), lignocaine (100 µM) and cadmium (0.2 mM; but not manganese, 1 mM) blocked I Na2 . During fast depolarizing ramps, the rapid inactivation of I Na1 was followed by a negative slope region. During repolarizing ramps, a region of positive slope was present, whereas I Na1 was absent. At less negative values of V h , the amplitude of the negative and positive slopes became gradually smaller. Gradually faster ramps increased the magnitude of the negative slope, and tetrodotoxin (30 µM) reduced or abolished it. Thus, Purkinje cells have a slowly decaying inward current owing to Na + entry (I Na2 ) that is different in several ways from the fast I Na1 and that appears important for the duration of the plateau.