Selective inhibition of electrical conduction within the pulmonary veins by α1-adrenergic receptors activation in the Rat

Figures

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  Figure 1. (A) The electrode array position for recording from the LA (E1 to E4) along the right superior PV (RSPV, E5 to E8) on a representative preparation (LSPV and RSPV: left and right superior pulmonary vein, LA and RA: left and right atria, LAA: left atria appendage). (B) An example of EFP recordings obtained from an array positioned as shown in A under basal conditions and during spontaneous sinus rhythm (330 bpm). The activation time for each electrode (ms) relative to E4 which was the first that detected a signal (indicated by arrows) is shown to the right.

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  Figure 2. (A) A representative recording of electrical activity in a preparation driven by sinus rhythm during the superfusion of 3 × 10−8 and 10−7 M cirazoline. The position of the array was that shown in Fig. 1A. Conduction was lost first in the distal PV (E8) and then progressively down the length of the vein (E7 to E5). Conduction across the LA (E4 to E1) was maintained. (B) Reversal of the effect of cirazoline with prazosin. In a different preparation driven by sinus rhythm, the superfusion of 10−7 M cirazoline had led to the loss of conduction along the PV (E4 to E8) while retaining conduction across the LA (E4 to E1). The addition of 5 × 10−6 M prazosin in the continued presence of cirazoline, led to the progressive recovery of conduction along the PV from its base (E4) to its distal part (E8).

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  Figure 3. (A) Conduction across the LA and along the PV in a preparation driven by 5 Hz electrical stimulation applied to the base of the LAA. In 3 × 10−8 M cirazoline conduction was maintained across the LA (E1 to E4) while conduction along the PV (E5 to E8) was lost. (B) Effect of cirazoline upon the conduction velocity of electrical signals evoked by stimulation in the LAA. The application of cirazoline led to the progressive reduction of conduction velocity (measured as the time taken for the signal to pass between 2 adjacent electrodes) prior to the loss of the electrical signal between E5 to E8 in the distal PV. This decrease was less pronounced at the junction between PV and LA (between E5 to E3) and was not observed in the LA (between E3 to E1) (n = 5, **p < 0.01, ***p < 0.001 vs 0 min, standard error bars have been omitted for clarity). (C) When electrical stimulation was applied to the distal PV, cirazoline (3 × 10−8 M) blocked conduction not only along the vein (E8 to E5) but also across the LA (E4 to E1).

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  Figure 4. (A) Simultaneous intracellular microelectrode recordings from the PV (left) and the LA (right) in one preparation during the superfusion of 10−6 M cirazoline. Pairs of AP are shown at one minute intervals from an otherwise continuous recording stimulated at 5 Hz. (B) The effects of 10−6 M cirazoline upon DMP (left) and AP amplitude (right) of electrically evoked AP recorded simultaneously in the LA (square symbols) and PV (round symbols). Symbols represent mean ± SEM of results obtained from 14 different preparations which were electrically paced at 5 Hz in the LA. ***p < 0.001 vs basal conditions. ns: no significant difference vs basal condition.

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  Figure 5. (A) A representative recording of electrical activity in the LA of a preparation driven by sinus rhythm from the right atrium (240 beats/min). The position of the electrode array is indicated in (E). (B) Conduction across the LA in the same preparation driven by 10 Hz electrical stimulation applied to the distal PV under control conditions. (C) After 9 minutes of superfusion of 10−6 M cirazoline, electric stimulation to the PV failed to evoke one-to-one EFP and conduction within the LA. (D) 1 minute later, the 10 Hz electrical stimulation to the PV failed to drive the preparation and conduction from the sinus node was restored within the LA. Stimulus artifacts and EFP are indicated by stars and arrows respectively in (B–D). (E) X indicates the position of the stimulation electrodes used in this series of experiments.

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  Figure 6. (A) The time course of the recovery of conduction in the PV induced by 5 × 10−5 M adenosine. In this preparation which was driven by sinus rhythm, conduction in the PV had been lost after 25 min exposure to 3 × 10−8 M cirazoline. The addition of adenosine induced the progressive development of conduction along the PV from its base (E4) to its distal part (E8) in 40 seconds. (B) Segments of a continuous recording of 5 Hz stimulated AP recorded with intracellular microelectrodes simultaneously from the PV (left) and the LA (right) during the superfusion of 10−6 M cirazoline and then the addition of 10−3 M of adenosine. (C) The effects of 10−3 M adenosine upon DMP (left) and AP amplitude (right) of PV (round symbols) and LA (square symbols) AP in the continuous presence of 10−6 M cirazoline. Symbols represent mean ± SEM of results obtained from 6 different preparations which were electrically paced at 5 Hz in the LA. ***p < 0.001 vs cirazoline.