Central nervous regulatory mechanism of myocardial ischemia-reperfusion injury in rats: excitability of neurons in hypothalamic paraventricular nucleus

Abstract

Objective To evaluate the relationship between excitability of neurons in hypothalamic paraventricular nucleus(PVN) and central nervous regulatory mechanism of myocardial ischemia-reperfusion(I/R) injury in rats. Methods Clean-grade healthy adult male Sprague-Dawley rats, in which PVN catheters were successfully implanted, aged 6-8 weeks, weighing 260-300 g, were divided into 4 groups(n=6 each) using a random number table method: sham operation group(S group), myocardial I/R group(I/R group), γ-aminobutyric acid group(GABA group) and L-glutamic acid group(L-Glu group). Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion. Normal saline 2.4 μl/h was infused for 50 min via the PVN catheter starting from 10 min before ischemia in S and I/R groups. GABA 30 μmol/L and L-glutamic acid 30 μmol/L were infused for 50 min via the PVN catheter at a rate of 2.4 μl/h starting from 10 min before ischemia in GABA and L-Glu groups. The heart rate(HR) and mean arterial pressure(MAP) were recorded at 10 min before ischemia(T0), beginning of ischemia(T1), 30 min of ischemia(T2) and 120 min of reperfusion(T3). Rate-pressure product(RPP) was calculated. Blood samples were collected at T3 for determination of plasma cardiac troponin I(cTnI) concentrations by chemiluminescence assay. Rats were then sacrificed and myocardial specimens were obtained for measurement of myocardial infarct size(IS) and area at risk(AAS), and IS/AAR percentage was calculated. PVN tissues were taken to detect the expression of c-fos by Western blot. Results No myocardial infarction was found in group S, and myocardial infarction was marked in the other three groups. Compared with group S, the plasma cTnI concentrations were significantly increased, and the expression of c-fos in PVN was up-regulated in I/R, GABA and L-Glu groups(P<0.05), and MAP, HR and RPP were significantly decreased at T1-3 in I/R and GABA groups and at T3 in group L-Glu(P<0.05). Compared with group I/R, IS and IS/AAR percentage were significantly decreased, the plasma cTnI concentrations were decreased, the expression of c-fos in PVN was down-regulated, and HR, MAP and RPP were decreased at T1, 2 in group GABA, and IS and IS/AAR percentage were significantly increased, the plasma cTnI concentrations were increased, the expression of c-fos in PVN was up-regulated, and HR, MAP and RPP were increased at T1, 2 in group L-Glu(P<0.05). Conclusion Excitability of neurons in hypothalamic PVN is involved in central nervous regulatory mechanism of myocardial I/R injury in rats: decreased excitability can attenuate myocardial I/R injury and increased excitability aggravates myocardial I/R injury. Key words: Paraventricular hypothalamic nucleus; Neurons; Myocardial reperfusion injury