Attenuation Of Myocardial Ischemia Research Articles

The effect of Simvastatin in attenuation of Myocardial Ischemia/ Reperfusion injury

Background: Myocardial ischemia–reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia–reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocytes damage.Objective: This study was undertaken to investigate the potential role of simvastatin in amelioration of myocardial I/R injury induced by ligation of coronary artery in a rat model. Materials & methods: adult male Swiss Albino rats were randomized into 4 equal groups. Group (I) sham group: rats underwent the same anesthetic and surgical procedure as the control group except ligation of LAD coronary artery , Group(II) control group: rats subjected to regional ischemia for 25 min by ligation of LAD coronary artery and reperfusion for 2 hours ,Group(III ) control vehicle group: rats received vehicle of simvastatin (normal saline) via I.P injection and subjected to regional ischemia for 25 min by ligation of LAD coronary artery and reperfusion for 2 hours , Group(IV) simvastatin treated group :rats pretreated with simvastatin 1mg/kg i.p 1 hr before ligation of LAD coronary artery. At the end of experiment (2 hr of reperfusion), the heart was harvested and the part of the heart just below the site of ligation was divided into two parts ,the upper part was homogenized for the measurement of interleukin-1β (IL-1β) and the lower part of tissues fixed in 10% formalin and embedded in paraffin the sections were stained with hematoxylin and eosin (H&E) then used for histopathological study .Results: Compared with the sham group, levels of myocardial IL-1β, were increased (p<0.001) in the control group. Simvastatin significantly counteract the increase in myocardium level of IL-1B (P < 0.001). Histological analysis revealed that simvastatin markedly reduced (P < 0.001) the severity of cardiac injury in the rats underwent LAD ligation procedure .Conclusions:The results of the present study reveal that simvastatin may ameliorate myocardial I/R injury in rats via interfering with inflammatory responses which induced by I/R injury.

Characterization of the warm-up phenomenon in patients with coronary artery disease

Background The warm-up phenomenon, that is, attenuation of myocardial ischemia during repeated physical exercise, has been demonstrated in numerous studies. However, its duration and underlying factors have not been properly studied in patients with coronary artery disease. Methods Fifty-two patients with stable angina pectoris and previous positive stress testing underwent cardiac catheterization and 2 successive exercise tests randomly separated by resting periods of 15, 30 , 60, or 120 minutes (groups 1-4). Results The percentage of patients demonstrating the warm-up phenomenon was 85%, 31%, 31%, and 46% in groups 1 through 4, respectively (P =.018). The differences in the parameters (test 2 to test 1) registered during exercise tests were 28.1 ± 7.1, 3.5 ± 5.8, −4.9 ± 4.8, and 4.9 ± 5.1 (P =.003) for the double product (beats/min × mm Hg · 100) at 0.1 mV ST depression; 1.1 ± 0.2, 0.2 ± 0.2, 0.2 ± 0.2, and 0.2 ± 0.2 (P =.004) for the time (min) to 0.1 mV ST depression; −3.4 ± 1.2, 0.5 ± 0.7, −0.3 ± 0.8, and −0.3 ± 0.3 (P =.032) for the ST/HR-slope (μV/beats/min); and −0.3 ± 0.2, 0.1 ± 0.1, −0.1 ± 0.1, and −0.7 ± 0.4 (P =.047) for the ischemic burden (mV × min) in groups 1 through 4, respectively. The patients having angiographically less severe disease showed significantly better ischemia adaptation (P =.012), but there was no correlation between the extent of adaptation and other clinical or angiographic findings. Conclusions The warm-up phenomenon is commonly encountered in patients with coronary artery disease, although the protection appears to wane relatively quickly. The adaptation appears to be markedly better in patients with less severe disease. (Am Heart J 2002;144:870-6.)

Transplantation of endothelial progenitor cells for therapeutic neovascularization

Endothelial progenitor cells (EPCs), which were first identified in adult peripheral blood mononuclear cells (MNCs), play an important role in postnatal neovascularization. Tissue ischemia augments mobilization of EPCs from bone marrow into the circulation and enhances incorporation of EPCs at sites of neovascularization. Two methods to obtain EPCs from bone marrow, peripheral blood or cord blood MNCs have been evaluated for therapeutic neovascularization: (1) fresh isolation using anti-CD34, anti-KDR or anti-AC133 antibody, and (2) ex vivo expansion of total MNCs. In an immunodeficient mouse model of hindlimb ischemia, systemic transplantation of human ex vivo expanded EPCs improves limb survival through the enhancement of blood flow in the ischemic tissue. A similar strategy also leads to histological and functional preservation of ischemic myocardium of nude rats. Recently, a preclinical study of catheter-based, intramyocardial transplantation of autologous EPCs in a swine model of chronic myocardial ischemia demonstrated the therapeutic potential of cell-based therapy, with attenuation of myocardial ischemia and improvement in left ventricular function. These favorable outcomes strongly suggest a therapeutic impact of EPC transplantation in clinical settings. Further basic research, with improved understanding of the mechanisms governing homing and incorporation of EPCs, will be still necessary to optimize the methodology of the cell therapy.

Attenuation of myocardial ischemia during coronary occlusion by ultrashort-acting beta adrenergic blockade: Labovitz AJ, Barth C, Castello R, et al Am Heart J 121:1347–1351 May 1991

Attenuation of myocardial ischemia during coronary occlusion by ultrashort-acting beta adrenergic blockade: Labovitz AJ, Barth C, Castello R, et al Am Heart J 121:1347–1351 May 1991

Attenuation of myocardial ischemia during coronary occlusion by ultrashort-acting beta adrenergic blockade

To assess the effect of the ultrashort-acting beta blocker esmolol on ischemia induced by acute coronary occlusion, we studied 16 patients undergoing coronary angioplasty. Doppler echocardiography and ECG monitoring were performed continuously before, during, and after balloon occlusion in the drug-free state and during esmolol infusion. Fourteen of the 16 patients had ST segment elevation during balloon inflation. However, maximal ST segment elevation (2.1 ± 1.5 mm vs 1.7 ± 1.3 mm, p < 0.001) and duration of ST segment elevation (68 ± 20 seconds vs 54 ± 19 seconds, p < 0.05) were both significantly reduced during esmolol infusion. Furthermore, the decrease in ejection fraction seen during drug-free balloon occlusions was significantly blunted during esmolol infusion. In the baseline state ejection fraction decreased from 55% to 38% ( p < 0.05) during coronary occlusion compared with a decrease from 52% to 49% ( p = NS) during esmolol infusion. In addition, esmolol appeared to delay the onset of segmental wall motion abnormalities after coronary occlusion, occurring at a mean of 40 seconds after balloon inflation versus a mean of 31 seconds in the absence of beta blockade ( p < 0.05). Thus the use of ultrashort-acting beta blockade appears to diminish the extent and delay the onset of myocardial ischemia during acute coronary occlusion.