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Objective To investigate the effects of sevoflurane postconditioning on myocardial ischemiareperfusion(I/R)injury in patients undergoing coronary artery bypass grafting(CABG)with cardiopulmonary bypass(CPB).Methods Forty NYHA Ⅰ -Ⅲ patients of both sexes,aged 55-64 yr,with BMI ＜ 30 kg/m2,scheduled for CABG under CPB,were randomly divided into 2 groups(n = 20): control group(group C)and sevoflurane postconditioning group(group S).Anesthesia was induced with midazolam and/or etomidate,fentanyl and rocuronium.Patients were tracheal intubated and mechanically ventilated.Anesthesia was maintained with iv infusion of propefol and intermittent iv injection of fentanyl and pipecuronium.In group S,2% sevoflurane was inhaled continuously for 15 min immediately after aortic unclamping.After anesthesia induction,before CPB,10 min after the end of CPB,at the end of operation,and 6 and 24 h after operation,MAP,HR,CVP,mean pulmonary arterial pressure,pulmonary arterial wedge pressure,CO and S(v)O2 were recorded,and CI,SVI,systemic vascular resistance index and pulmonary vascular resistance index were calculated.Blood samples were taken from central vein before aortic clamping,at 6 h of reperfusion and 24 h after operation for determination of plasma creatine kinase(CK),creatine kinase isoenzyme(CK- M B)and lactate dehydrogenase(LDH)activities and tropenin I(TnI)concentrations.Myocardial tissues were obtained from right auricle before aortic clamping and at the end of CPB for observation of the ultrastructure and the severity of myocardial injury was assessed.Results There was no significant difference in hemodynamics and parameters of cardiac function between the two groups(P ＞ 0.05).Compared with group C,plasma CK-MB and LDH activities at 6 h of reperfusion and plasma CK activity and TnI concentrations at 24 h after operation were significantly decreased and the myocardial injury was significantly reduced after the end of CPB in group S(P ＜ 0.05).Conclusion Sevoflurane postconditioning can protect myocardium against I/R injury induced by CPB in patients undergoing CABG.
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<p><b>OBJECTIVE</b>To investigate the effects of Salvia miltiorrhiza (SM) extracts on the expression of heme oxygenase-1 (HO-1) and nitric oxide synthase (NOS) in small pulmonary arteries (SPAs) of rats with chronic hypoxia.</p><p><b>METHODS</b>After two weeks of hypoxia, rats were treated with diltiazem, and small, median, and large doses of SM extracts. The lungs were tested for the expression and distribution of HO-1, endothelial NOS (eNOS) and inducible NOS (iNOS) by using immunohistochemistry and Western blot method.</p><p><b>RESULTS</b>Median and large doses of SM extracts significantly reduced hypoxia-induced media thickening in the SPAs (similar with diltiazem), recovered repaired ultrastructure injury, decreased HO-1 and iNOS levels, and increased eNOS expression in the SPAs.</p><p><b>CONCLUSIONS</b>Median and large doses of SM extracts play significant roles in inhibiting structural remodeling in rats with hypoxic pulmonary hypertension. These effects might attribute to the suppression of HO-1 and iNOS, and the promotion of eNOS expression under the conditions of hypoxia.</p>
Subject(s)
Animals , Rats , Drugs, Chinese Herbal , Pharmacology , Heme Oxygenase (Decyclizing) , Metabolism , Heme Oxygenase-1 , Hypertension, Pulmonary , Drug Therapy , Hypoxia , Nitric Oxide Synthase , Metabolism , Rats, Wistar , Salvia miltiorrhiza , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To evaluate the diagnostic value of dobutamine stress magnetic resonance imaging (MRI) for myocardial viability.</p><p><b>METHODS</b>Ten male miniswines underwent left ventriculography and coronary angiography, followed by stenosis of the left circumflex coronary artery (LCX) using ameroid constrictor. More than one month later, left ventriculography and coronary angiography were performed again, followed by cine-MRI at rest and during stress with incremental dose of dobutamine 5 - 20 micro g.kg(-1).min(-1). Traditional and/or breath-hold cine-MRI were used to evaluate regional left ventricular wall motion, corresponding to basal, midventricular and apical short-axis tomograms. Regional wall motion score index (WMSI) was calculated. The miniswines were finally sacrificed for pathological examination. Triphenyl tetrazolium chloride (TTC) delineated myocardial infarction. Microscopy was used to identify myocardial cellular changes.</p><p><b>RESULTS</b>One pig died, one pig suffered from aneurysm and another showed no negative findings. The other seven pigs were found with hypokinetic (n = 4) or akinetic (n = 3) myocardial regions related to stenosed LCX. Their mean WMSI at rest for the lateral and posteroinferior walls (ischemic regions) of the left ventricle was 2.27 +/- 0.32, as compared with 1.00 +/- 0.00 (P < 0.01) for the corresponding nonischemic anteroseptal regions. Further, the mean WMSI for the ischemic regions was 2.27 +/- 0.32 at rest compared with 1.40 +/- 0.39 (P < 0.01) at the dose of dobutamine 5 micro g.kg(-1).min(-1). However, the mean WMSI at the doses of dobutamine 10 and 20 micro g.kg(-1). min(-1) were 1.70 +/- 0.76 and 1.75 +/- 0.83, respectively, with no significant difference as compared with the mean WSCI at rest (P > 0.05). The pathologic examination showed viable myocardium at the ischemic regions.</p><p><b>CONCLUSION</b>Low-dose dobutamine (5 micro g.kg(-1).min(-1)) recovers hypokinetic or akinetic myocardial regions, and dobutamine stress MRI can be used to detect myocardial viability.</p>
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Animals , Male , Dobutamine , Magnetic Resonance Imaging, Cine , Methods , Swine , Swine, Miniature , Ventricular Function, LeftABSTRACT
<p><b>OBJECTIVE</b>To compare the effects of high, middle and low doses of enalapril in preventing left ventricular remodeling (LVRM) after acute myocardial infarction (AMI) in rats, especially evaluating the efficacy of low dose enalapril.</p><p><b>METHODS</b>AMI was induced by ligating the left coronary artery in 149 female SD rats. 48 hours after the procedure, the 97 surviving rats were randomized to one of the following four groups: (1) AMI controls (n = 24), (2) high-dose (10 mg x kg(-1) x d(-1), n = 25), (3) middle-dose (1 mg x kg(-1) x d(-1), n = 23), and (4) low-dose (0.1 mg x kg(-1) x d(-1), n = 25) enalapril groups. In addition, sham-operated (n = 13) and normal rats (n = 10) were randomly selected to serve as non-infarction controls. Enalapril was delivered by direct gastric gavage. After 4 weeks of therapy, hemodynamic studies were performed, then the rat hearts were fixed with 10% formalin and pathology analysis was performed. Exclusive of the dead rats and those with MI size < 35% or > 55%, complete experimental data were obtained from 67 rats, which were comprised of (1) AMI controls (n = 13), (2) high-dose enalapril (n = 13), (3) middle-dose enalapril (n = 12), (4) low-dose enalapril (n = 12), (5) sham-operated (n = 8) and (6) normal (n = 9) groups.</p><p><b>RESULTS</b>There were no significant differences among the four AMI groups in infarction size (all P > 0.05). Compared with the sham-operated group, the left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), absolute and relative weight (LVAW, LVRW) in AMI group were all significantly increased (all P < 0.001), while maximum LV pressure rising and dropping rates (+/- dp/dt) and their corrected values by LV systolic pressure (+/- dp/dt/LVSP) were all significantly reduced in the AMI control group (P < 0.01 - 0.001), indicating LVRM occurred and LV systolic and diastolic functions were impaired. Compared with the AMI group, LVEDP, LVV, LVAW and LVRW were all significantly decreased in the three enalapril groups (control P < 0.001), with the reduction of LVEDP, LVV and LVAW being more significant in high-dose than in low-dose enalapril groups (all P < 0.05), and the +/- dp/dt/LVSP were significantly increased only in the high and middle-dose enalapril groups (P < 0.01).</p><p><b>CONCLUSIONS</b>High, middle and low doses of enalapril were all effective in preventing LVRM after AMI in the rat, with low dose enalapril being effective and high dose superior. As for LV functional improvement, only high and middle-dose enalapril were effective.</p>
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Animals , Female , Rats , Angiotensin-Converting Enzyme Inhibitors , Pharmacology , Dose-Response Relationship, Drug , Enalapril , Pharmacology , Myocardial Infarction , Rats, Sprague-Dawley , Ventricular RemodelingABSTRACT
Objective To observe the morphological changes of brain and to analyze the cause of coma after open-heart surgery in cases suffered from congenital heart disease. Methods Twenty six autopsy cases were collected from Jan. 1973 to Sep. 1999 in Fuwai Hospital. Their duration of coma was 1 day to 40 days and all of them died earlier later following cardiac surgery. Their surgical procedure, extracorporeal circulation time, and other clinical records and autopsy findings were reviewed. Results The brain lesions included intracranial hemorrhages (n＝11), cerebral edema (n＝11), encephalitis and encephalomingitis (n＝3), and cerebromalacia (n＝1). Intracranial hemorrhages occurred in epidural (n＝3), subdural (n＝3), subarachoid spaces (n＝4), and intracerebral parenchyma (n＝1). The causes of coma were deduced as follows: lower cardiac output (n＝7), air embolism (n＝3), pneumonia (n＝3) and other infections (n＝2), pulmonary hypertension (n＝2), and the unknown causes of coma (n＝9). But the 6 out of the last 9 cases showed longer duration (more than 100 min) of extracorporeal circulation. Intracranial hemorrhages occurred more frequently in cases with waking period than those without after cardiac operation, and vice versa the cerebral edema. Conclusion Intracranial hemorrhage and cerebral edema were the main changes of brain in the patients suffered from coma, but its causes were complex and difficult to analyze. These results suggest that further improved heart preservation, shorter time of extracorporeal circulation and effective treatment of infection would be benefit to the prevention of coma.
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AIM: To compare the protective effects of tongxinluo, a Chinese medicine, and carvedilol and valsartan on myocardium microvascular endothelial function and integrity after late reperfusion of acute myocardial infarction (AMI) in rabbits. METHODS: Forty-eight rabbits were randomly assigned to the following groups: (1) sham operated rabbits; (2) ischemia-reperfusion (I-R) controls; (3) tongxinluo (1.0 g?kg~ -1?d~ -1); (4) carvedilol (5 mg?kg~ -1?d~ -1); (5) valsartan (10 mg?kg~ -1?d~ -1) and (6) ticlopidine + aspirine (30 and 20 mg?kg~ -1?d~ -1, respectively) groups. After 3 d of drug treatment, the left coronary artery in the rabbit was ligated for 2 h and loosed subsequently for another 2 h. The serum levels of nitric oxide (NO_2~-/NO_3~-) and endothelin (ET) at baseline before AMI, 2 h after both AMI and reperfusion were examined. Also, the number of circulating endothelial cells (CEC), MI size and percentage myocardium focal bleeding incidence were determined 2 h after reperfusion. RESULTS: (1) The baseline level of NO_2~-/NO_3~- was significantly higher in tongxinluo group than that in other groups (all P
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0 05) Left ventricular (LV) end diastolic pressure (LVEDP), volume (LVV), weight (LVW) and septal thickness (STh) were all higher and left ventricular pressure maximal rate of rise and fall (?d p /d t ) were lower (all P
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Objective To establish the chronic low flow myocardial hibernation animal model in pigs, and to assess the diagnostic value for myocardial hibernation by using various imaging methods. Methods A total of 13 miniswine (30-40 kg) were used. All animals underwent general anesthesia and orotracheal intubation while the animals were mechanically ventilated. Under sterile conditions, left ventriculography and coronary angiography were performed by introduction of catheter into the right femoral artery. Further, a left anterolateral thoracotomy was performed in the third intercostal space. The proximal LCX was dissected free to allow placement of an ameroid constrictor. More than 1 month later, left ventriculography and coronary angiography were performed again, followed by cine MRI at rest and during stress with low dose of dobutamine (5 ?g?kg -1 ?min -1 ), respectively. Traditional and/or breath hold cine MRI were used to evaluate regional left ventricular wall motion, corresponding to basal, midventricular and apical short axis tomograms. Regional wall motion score index (WMSI) was calculated. At the same time 99m Tc MIBI myocardial SPECT was performed at rest and during nitroglycerin administration, respectively. All animals were finally sacrificed for pathological examination. Triphenyl tetrazolium chloride (TTC) staining was used to assess the myocardial infarction. Electron microscopy was used to identify myocardial cellular changes characteristic of hibernating myocardium. Results Three pigs died during surgery or within two weeks after surgery. One pig died of anesthesia during SPECT examination, 1 pig suffered from aneurysm, and another one pig showed negative findings. The other 7 pigs were found with hypokinetic ( n =4) or akinetic ( n =3) myocardial regions related to stenosed LCX (70%-99%). Resting cine MRI demonstrated decreased regional motion of the lateral and posteroinferior walls (ischemic regions) of the left ventricle ( n =7), compared with the nonischemic anteroseptal regions; but the low dose dobutamine (5 ?g?kg -1 ?min -1 ) could recover those hypokinetic or akinetic myocardial regions, characteristic of hibernating myocardium. Resting 99m Tc MIBI myocardial SPECT ( n =6) showed a fixed perfusion defect on the corresponding ischemic areas, which became reversible on the nitrate augmented myocardial perfusion imaging. It also indicated myocardial viability presented at the ischemic areas. TTC staining revealed patchy infarction of the area at risk localized to the endocardial surface ( n =3), and no myocardial infarction ( n =4). Electron microscopy of sections from the hibernating regions revealed loss of contractile materials, increased numbers of small mitochondria, and glycogen accumulation within viable cardiomyocytes, which had been described as hallmarks of hibernating myocardium. Conclusion Chronic low flow myocardial hibernation can be reproduced in an animal model during progressive coronary stenosis caused by ameroid constrictor.
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Objective To study the protective effect of Xinfuli Granula(XG) on acute and chronic cardiac failure in cats and rats. Methods The cat models of acute cardiac failure were established by injecting pentobarbital. Then the cat models were given XG through duodenum. After medication,hemodynamics parameters such as heart rate(HR),mean arterial pressure(MAP),left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),+ dp/dtmax and cardiac output(CO) in cats were determined. The rats were divided randomly into 5 groups:the control group,the model group,the positive control group,and high-dose and Low-dose XG groups. The rat models of myocardial injury were induced by isoproterenol(20 mg/kg). The normal group and the model group were treated with normal saline(10 mL/kg) orally,the positive contral group were treated with cedilanid(0.2 mg/kg) by intravenous,the high-and low-dose XG groups were orally treated with XG(10 g/kg and 5 g/kg respectively),and the propranolol group was orally treated with propranolol(4 mg/kg),once a day for successive 8 days. Animals were sacrificed on the 9th day,then the heart was taken out and the cardiac index was calculated. The pathological changes in myocardial cells of the rats were observed under electron microscope. Results XG had no effect on hemodynamics of cats with acute cardiac failure,but had obvious protective and therapeutic effect on isoproterenol-inducedmyocardial injury and myocardial ischemia of rats. Conclusion Xinfuli Granula has good preventive effect on isoproterenol-induced myocardial injury and sub-acute cardiac failure of rats,but has no effect on acute cardiac failure of cats.
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AIM: To investigate the action of diltiazem (a calcium antagonist) on the expression of heme oxygenase (HO) -1 and nitric oxide synthase (NOS) in the small pulmonary arteries (SPA) of rat in chronic hypoxia. METHODS: Chronic pulmonary arterial hypertension models were established by treating the rats in hypoxic environment[(10%?1%)O 2] for 6 weeks. After 2 weeks of hypoxia, rats were treated with diltiazem (15 mg/kg/day). Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were measured. Pathological changes in the lungs were observed under the light microscope and transmission electron microscope. The expression and distribution of heme oxygenase (HO) -1, endothelial NOS (eNOS) and inducible NOS (iNOS) were tested by immunohistochemistry and Western blot. Guanosine-3', 5'-cyclic monophosphate (cGMP) of lung tissues were detected with radioimmunoassay. RESULTS: Diltiazem significantly decreased abnormal RVSP, and RVHI in model rats, attenuated the SPA media thickeness, and recovered abnormal eNOS and iNOS expression in SPA. Whereas diltiazem had little effect on the increased HO-1 expression in SPA caused by hypoxia and ultrastructure injury in endothelium. cGMP levels were corresponded with HO-1. CONCLUSION: Diltiazem has a significant effect on inhibiting hypoxic pulmonary hypertension structural remodeling. These effects might be partly attributed to the suppression of iNOS, promotion of eNOS, and not attenuation HO-1 expression in the lung of hypoxic rats.