Role of β-Adrenergic Signal Transduction Pathway on Myocardial Ischemic Preconditioning of Rats

To study the changes in every part of the β-adrenergic signal transduction pathway and their effects on ischemic preconditioning of rat myocardium in vivo. SD rats were divided into three groups： IP group, I/R group and CON group. The IP group was further divided into PC1-, 2-, 3-, and PC1＋, 2＋, 3＋ groups according to preconditioning procedure. The rats received surgical procedure and underwent left coronary artery occlusion and reperfusion. We analyzed the infarct size by TTC staining, measured serum myocardial enzymes, studied the β-AR Bmax and Kd by radioligand binding assay of receptors, checked the activity of AC and PKA by the method of biochemistry and examined the content of cAMP by radioimmunoassay. The infarct area was much smaller in the IP group than in the I/R group （P〈0. 001）, while the enzymes were significantly higher in I/R （P〈0. 001）. The Bmax of β-AR in IP was much higher than that in I/R （P〈0. 001）, but no difference in Kd could be seen between IP and I/R groups. In IP, the activity of AC and PKA and the content of cAMP were higher than those in I/R （P〈0.05, 0. 002 and 0. 001, respectively）. In the procedure of preconditioning, the content of cAMP and the activity of PKA showed the characteristic of cyclic fluctuation. Ischemic preconditioning can protect the heart from necrosis and reduce endo-enzyme leakage. The system of β-adrenergic signal transduction pathway probably takes part in the protection effect of the IP, which might be elicited by the PKA .

EFFECTS OF GLIBENCLAMIDE, GLIMEPIRIDE, AND GLICLAZIDE ON ISCHEMIC PRECONDITIONING IN RAT HEART

Objective To compare the influence of different sulfonylureas on the myocardial protection effect of ischemic preconditioning (IPC) in isolated rat hearts, and ATP-sensitive potassium channel current (IKATP) of rat ventricular myocytes. Methods Isolated Langendorff perfused rat hearts were randomly assigned to five groups: (1) control group, (2) IPC group, (3) IPC+glibenclamide (GLB, 10 μmol/L) group, (4) IPC+glimepiride (GLM, 10 μmol/L) group, (5) IPC+gliclazide (GLC, 50 μmol/L) group. IPC was defined as 3 cycles of 5-minute zero-flow global ischemia followed by 5-minute reperfusion. The haemodynamic parameters and the infarct size of each isolated heart were recorded. And the sarcolemmal IKATP of dissociated ventricular myocytes reperfused with 10 μmol/L GLB, 1 μmol/L GLM, and 1 μmol/L GLC was recorded with single-pipette whole-cell voltage clamp under simulated ischemic condition. Results The infarct sizes of rat hearts in IPC (23.7%±1.3%), IPC+GLM (24.6%±1.0%), and IPC+GLC (33.1%±1.3%) groups were all significantly smaller than that in control group (43.3%±1.8%; P<0.01, n=6). The infarct size of rat hearts in IPC+GLB group (40.4%±1.4%) was significantly larger than that in IPC group (P<0.01, n=6). Under simulated ischemic condition, GLB (10 μmol/L) decreased IKATP from 20.65±7.80 to 9.09±0.10 pA/pF (P<0.01, n=6), GLM (1 μmol/L) did not significantly inhibit IKATP (n=6), and GLC (1 μmol/L) decreased IKATP from 16.73±0.97 to 11.18±3.56 pA/pF(P<0.05, n=6). Conclusions GLM has less effect on myocardial protection of IPC than GLB and GLC. Blockage of sarcolemmal ATP-sensitive potassium channels in myocardium might play an important role in diminishing IPC-induced protection of GLM, GLB, and GLC.

Protective effects of hypovolemic hypotension preconditioning on cardiopulmonary function after myocardium ischemia/reperfusion injury

Objective: To identify the protective effects of hypovolemic hypotension preconditioning on cardiopulmonary function after myocardial ischemia/reperfusion injury and to explore the possible mechanism.Methods: Twenty-four male white rabbits were randomly assigned to two groups. In the control group, ischemia/reperfusion animals(Group I/R, n=10) were subjected to thirty-minute occlusion of left anterior descending coronary artery and two-hour reperfusion. Animals in hypovolemic hypotension preconditioning group (Group HHP, n=14) experienced brief systemic ischemia preconditioning through blood withdrawl to lower blood pressure to 40%-50% of the baseline before myocardial ischemia/reperfusion. Hemodynamic parameters were recorded. Blood sample was taken to measure superoxide dismutase (SOD), malondialdehyde (MDA) and nitrogen monoxide (NO) changes with blood gas analysis. Myocardium specimens were sampled to examine apoptosis-related gene interleukin-1 beta converting enzyme (ICE) mRNA. Results: Cardiac mechanical function and lung gas exchange remained stable in Group HHP with a significant increase in NO level; while in Group I/R without preconditioning, cardiopulmonary dysfunction was present after 2 h reperfusion associated with a significant reduction in NO formation and an increase in MDA (P<(0.001)). There was negative expression of ICE mRNA in the two groups.Conclusions: Hypovolemic hypotension preconditioning significantly improves cardiopulmonary function and increases NO formation and the protective benefit associated with hypovolemic hypotension preconditioning of the heart may be regulated through NO mediated mechanism.

远程预缺血的心肌保护机制

Remote myocardial preconditioning can protect myocardium. Some bioactive substances released from noncardiac tissues which suffer from ischemia and reperfusion protects the heart by neuronal and humoral paths. Preconditioning at a distance can attenuate myocardial intracellular acidosis and Ca2+ overload,reduce neutrophil and platelet infiltration, protect mitochondrial function and reduce free radicals. This method is simple to apply and have some clinical value. In order to safely apply this method to clinic, a further study on the remote myocardial preconditioning and its mechanism is necessary.