Table 2.

Summary of Different Experimental and Clinical Studies Concerning the Role of Funny Current During Sepsis and Heart Failure

Authors	Experimental / Clinical protocol	Major findings
Verkerk et al. [64]	SAN cells from control rabbits versus rabbits with volume and pressure overload-induced heart failure	Increased intrinsic CL and decreased diastolic depolarization rate, associated with a reduced density of If.
Zorn-Pauly and colleagues [66]	Effects of LPS on If in human myocytes isolated from atrial appendages of patients undergoing open-heart surgery.	Voltage-dependency of If activation was shifted to more negative potentials. Reduced response of IBI fluctuations to ANS stimuli after LPS-induced If impairment
Joannides et al. [68]	Healthy volunteers during tilt and exercise.	Ivabradien, a new selective If current blocker at the level of SAN, significantly decreased LF/HF ratio
BEAUTIfUL trial [72,73]	10.917 patients with CAD, LVEF < 40% and heart rate ≥ 60 beats/min	Ivabradien in patients with a heart rate of >70 beats/min decreased admission to the hospital for fatal and non-fatal myocardial infarction
MODIf Y trial [91]	Effects of Ivabradien in 70 critically ill patients with multiple organ dysfunction syndrome, with heart rate ≥ 90 beat/min and contradiction to beta-blockers	(still ongoing)
Schmidt and colleagues [92]	Impact of LPS upon HRV (SDNN, RMSSD), in monolayers of spontaneously contracting rat neonatal ventricular cardiomyocytes	1 µgr/mL of LPS significantly reduced SDNN, RMSSD and pNN50
Klöckner et al [94]	Transfected HEK cells with cDNA encoding the HCN2 channel proteins and incubated with LPS	Decrease in activation of If with reduced steepness of diastolic depolarization, occured within approximately 8 seconds