Temporal profile and mechanisms of the prompt sympathoexcitation following coronary ligation in Wistar rats

Our aim was to assess the timing and mechanisms of the sympathoexcitation that occurs immediately after coronary ligation. We recorded thoracic sympathetic (tSNA) and phrenic activities, heart rate (HR) and perfusion pressure in Wistar rats subjected to either ligation of the left anterior descending coronary artery (LAD) or Sham operated in the working heart-brainstem preparation. Thirty minutes after LAD ligation, tSNA had increased (basal: 2.5±0.2 µV, 30 min: 3.5±0.3 µV), being even higher at 60 min (5.2±0.5 µV, P<0.01); while no change was observed in Sham animals. HR increased significantly 45 min after LAD (P<0.01). Sixty minutes after LAD ligation, there was: (i) an augmented peripheral chemoreflex - greater sympathoexcitatory response (50, 45 and 27% of increase to 25, 50 and 75 µL injections of NaCN 0.03%, respectively, when compared to Sham, P<0.01); (ii) an elevated pressor response (32±1 versus 23±1 mmHg in Sham, P<0.01) and a reduced baroreflex sympathetic gain (1.3±0.1 versus Sham 2.0±0.1%.mmHg-1, P<0.01) to phenylephrine injection; (iii) an elevated cardiac sympathetic tone (ΔHR after atenolol: -108±8 versus -82±7 bpm in Sham, P<0.05). In contrast, no changes were observed in cardiac vagal tone and bradycardic response to both baroreflex and chemoreflex between LAD and Sham groups. The immediate sympathoexcitatory response in LAD rats was dependent on an excitatory spinal sympathetic cardiocardiac reflex, whereas at 3 h an angiotensin II type 1 receptor mechanism was essential since Losartan curbed the response by 34% relative to LAD rats administered saline (P<0.05). A spinal reflex appears key to the immediate sympathoexcitatory response after coronary ligation. Therefore, the sympathoexcitatory response seems to be maintained by an angiotensinergic mechanism and concomitant augmentation of sympathoexcitatory reflexes

Peripheral chemoreflex responses post LAD ligation.

<p>Three doses of sodium cyanide (0.03% solution; 25, 50 and 75 µL, i.a.) were given 60 min post LAD ligation and in Sham operated (n = 7 each group). (A) Recordings of a LAD rat (Ai) and a Sham rat (Aii) showing sympathoexcitation at all doses. (B) Change in sympathoexcitatory response (**P<0.01 compared to Sham). Difference in the magnitude of sympathoexcitation between doses used in the study (^#P<0.05 and ^##P<0.01). No changes in chemoreflex evoked responses in respiratory rate (C), pressor (D), and bradycardia (E).</p

Representative traces from rats showing LVP and transient ECG changes post LAD ligation.

<p>(A) Extra-systoles and tachycardia occurred post LAD ligation in some rats. (B) Atrioventricular block starting shortly post LAD ligation. These changes in the ECG lasted 34.0±4.6 min. (C) Median cross-sections of Evans blue dye-stained hearts. The LAD heart cross-section (left) had a safe blue-marked area versus a myocardial area at risk that did not absorb the dye (outlined pale area), contrasting with the Sham heart completely stained blue. (D) Recording showing LVP before and 1, 30, and 60 min post LAD ligation.</p

Baroreceptor reflex responses post LAD ligation.

<p>Phenylephrine (30 µg, i.a.) was given 60 min post LAD ligation and in Sham rats (n = 6 each group). (A) and (B) Changes in phenylephrine evoked pressor response and sympathetic gain (**P<0.01 compared to Sham). (C) No change in bradycardic gain.</p

Hemodynamic parameters before and minutes after LAD ligation in(n = 7).

<p>*P<0.05 and **P<0.01 compared to Before. LVSP, left ventricular systolic pressure; LVEDP, left ventricular end-diastolic pressure; LV dP/dT, maximum rate of LVP rise and fall.</p