Cardiac taurine levels during endotoxemia

Three hours after dogs were given an intravenous injection of Escherichia coli endotoxin significant decreases in cardiac taurine levels were observed in the apex and epicardial regions of the right ventricle and in all regions sampled from the left ventricle. A decrease in taurine was seen in all regions of the heart (including the atria) by 90 min after endotoxin treatment but the results were not statistically significant. Echocardiography and left ventricular cannulation were used in a separate group to confirm that the dose of endotoxin used was adequate to produce depression of cardiac output and force of contraction.     

The importance of myocardial amino acids during ischemia and reperfusion in dilated left ventricle of patients with degenerative mitral valve disease

Taurine, glutamine, glutamate, aspartate, and alanine are the most abundant intracellular free amino acids in human heart. The myocardial concentration of these amino acids changes during ischemia and reperfusion due to alterations in metabolic and ionic homeostasis. We hypothesized that dilated left ventricle secondary to mitral valve disease has different levels of amino acids compared to the right ventricle and that such differences determine the extent of amino acids' changes during ischemia and reperfusion. Myocardial concentration of amino acids was measured in biopsies collected from left and right ventricles before cardioplegic arrest (Custodiol HTK) and 10 min after reperfusion in patients undergoing mitral valve surgery. The dilated left ventricle had markedly higher (P < 0.05) concentrations (nmol/mg wet weight) of taurine (17.0 ± 1.5 vs. 10.9 ± 1.5), glutamine (20.5 ± 2.4 vs. 12.1 ± 1.2), and glutamate (18.3 ± 2.2 vs. 11.4 ± 1.5) when compared to right ventricle. There were no differences in the basal levels of alanine or aspartate. Upon reperfusion, a significant (P < 0.05) fall in taurine and glutamine was seen only in the left ventricle. These changes are likely to be due to transport (taurine) and/or metabolism (glutamine). There was a marked increase in the alanine to glutamate ratio in both ventricles indicative of ischemic stress which was confirmed by global release of lactate during reperfusion. This study shows that in contrast to the right ventricle, the dilated left ventricle had remodeled to accumulate amino acids which are used during ischemia and reperfusion. Whether these changes reflect differences in degree of cardioplegic protection between the two ventricles remain to be investigated.     

Alteration of collagenous protein profile in congestive heart failure secondary to myocardial infarction

The rat model of myocardial infarction is characterized by progressive cardiac hypertrophy and failure. Rats with infarcts greater than 30% of the left ventricle exhibited early and moderate, stages of heart failure 4 and 8 weeks after the occlusion of the left coronary artery, respectively. As heart failure is usually associated with remodeling of the extracellular matrix, a histological and biochemical study of cardiac collagenous proteins was carried out using failing hearts. Total collagen content in the right ventricle increased at 2, 4, and 8 weeks following occlusion of the left coronary artery whereas such a change in viable left ventricle was seen after 4 and 8 weeks. Total cardiac hydroxyproline concentration was increased in both right and left ventricular samples from the infarcted animals when compared to those of control; this increase was due to elevation of pepsin-insoluble collagen fraction. The myocardial noncollagenous/collagenous protein ratio was decreased in experimental right and left ventricular samples when compared to control samples. These findings suggest that an increase in cross-linking of cardiac collagen as well as disparate synthesis of collagenous and noncollagenous proteins occurs in this model of congestive heart, failure.     

Regional changes in ornithine decarboxylase activity and polyamine levels during thyroxine-induced cardiac hypertrophy

Ornithine decarboxylase activities (ODC) and polyamine levels were determined in five cardiac regions of the rat heart, following daily administration of 1 mg/kg of thyroxine, in the right and left atria, the right and left ventricles and the septum. The thyroxine stimulated ODC activity in all five regions of the heart. Enzyme activity in the left atrium and the septum peaked a day earlier than in other regions and the decline of ODC activity was slower. Putrescine in control animals was present in all regions except the right atrium, where its content was below detectable levels. Following the administration of thyroxine, the putrescine content of the left atrium, the right ventricle and the septum declined, while spermidine and spermine levels remained unchanged. In direct contrast to the other regions of the heart, thyroxine stimulated an increase in polyamines, as well as in weight which occurred exclusively in the left ventricle. These findings suggest a causal relationship between increased polyamines and hypertrophy.     

IP3 type 1 receptors in the heart: their predominance in atrial walls with ganglion cells

Previously we have shown that inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are abundantly expressed in the atria of rat hearts. Since arrangement of atria is very heterogeneous, in this work we focused on the precise localization of IP3 receptors in the left atrium, where the gene expression of the type 1 IP3R was the highest. The mRNA levels of the IP3 type 1 receptors in the left atrium, left ventricle and myocytes were determined using real-time polymerase chain reaction and Taqman probe. For precise localization, immunohistochemistry with the antibody against type 1 IP3Rs was performed. The mRNA of type 1 IP3 receptor was more than three times higher in the left atrium than in the left ventricle, as determined by real-time PCR. Expression of the type 1 IP3 receptor mRNA was higher in the atria, especially in parts containing cardiac ganglion cells. The atrial auricles, which are particularly free of ganglion cells, and the ventricles (wall of the right and left ventricle and ventricular septum) contained four to five times less IP3 receptors than atrial samples with ganglia. IP3R type 1 immunoreactivity detected by a confocal microscope attributed the most condensed signal on ganglionic cells, although light immunoreactivity was also seen in cardiomyocytes. These results show that type 1IP3 receptors predominate in intrinsic neuronal ganglia of cardiac atria.     

The Continuity of Right and Left Ventricular Myocardial Sinusoidal Spaces and its Relation to Right Ventricular Implants

Evidence is presented which indicates that blood leaving side branches of an internal mammary artery implanted into the anterior wall of the right ventricle flows from the tunnel in which it lies through myocardial sinusoidal spaces of the anterior right ventricular wall across the midline to fill corresponding spaces in the anterior wall of the left ventricle and thence is carried to the left coronary sinus. The myocardial sinusoidal spaces of right and left ventricles have been well outlined, using injections of polyvinyl acetate and the technique of digestion casts. We have been able to show that there is no barrier between the myocardial sinusoids of the right circulation and those related to the anterior descending branch of the left coronary artery. In structure, these myocardial sinusoidal spaces are quite different from the intramyocardial coronary arteriolar zones which, in 93% of human hearts, are separated from one another without collateral communication.The continuity of the right and left ventricular myocardial sinusoids explains why implantation of a right internal mammary artery into the anterior wall of the right ventricle combined with a corresponding left implant, epicardiectomy and free omental graft, has been so effective in our hands in the treatment of far-advanced human coronary artery insufficiency.     

Protection afforded by allopurinol in the first 24 hours of coronary occlusion is diminished after 48 hours

Experiments were performed to test whether the reduction in infarct size afforded by allopurinol following 24 h of permanent coronary artery occlusion is sustained over the subsequent 24 h. A dog's coronary artery was occluded with an embolus followed by injection of radiomicrospheres into the left ventricle to mark the ischemic region and to measure regional blood flow. Dogs were sacrificed either 24 h or 48 hours after embolization. The infarcts were delineated by failure to stain with triphenyl tetrazolium chloride and the ischemic zones were visualized by autoradiography of the heart slices. Dogs in the treatment groups received 600 mg of allopurinol PO 18 h before surgery, and a 10 mg/kg IV bolus 15 minutes before embolization followed by constant IV infusion of 55 mg/kg/24 h until sacrifice. A close correlation in the control animals between the percent of the ischemic zone which infarcted and collateral blood flow was used to predict a nonintervention infarct size in each treatment animal. Allopurinol treatment caused 17.9 +/- 3.3% less of the risk zone to be tetrazolium negative after 24 hours of ischemia than that seen in untreated animals. Less allopurinol induced salvage was observed in the 48 hour drug group with only a 11.1 +/- 3.3% limitation in infarct size. Furthermore, the effect was inconsistent at 48 h with only 2 dogs showing salvage. We conclude that allopurinol delays but does not prevent infarction in the permanent occlusion model.     

The effect of taurine on the density of adrenergic nerve endings and the recovery of cardiac function after ischemia

Isolated guinea-pig hearts perfused at 37 degrees C with Krebs-Henseleit buffer through aorta. Mechanical function was evaluated by isovolumic pressure in a latex balloon inserted into left ventricle. The density of catecholamine-containing adrenergic nerve plexus was measured in both ventricles after 40 min of total ischemia and 30 min of reperfusion. Heart preparations were treated with 2% glyoxylic acid and the relative area occupied by the plexus was determined alanimetrically. Without taurine (control) the adrenergic plexus density was 4-(right ventricule) and 6-fold (left ventricule) lower compared with that in freshly isolated hearts. When taurine was added to the perfusion solution after ischemia, the plexus density increased about 2.7-fold; if it was added prior to ischemia, the density was nearly equal to the original value. In no experiment with taurine addition during reperfusion fibrillation did occur, and about 2-fold more rapid restoration of regular rhythm was observed comparing with the control and experiments when taurine was added prior to ischemia. Both in the latter and control experiments spontaneously disappearing fibrillation occurred. The restoration of pressure and contraction frequency were virtually the same in all experiments. These findings show that taurine is able to preserve the catecholamine stores in the myocardium.     

Reduction of beta-adrenoceptor function by oxidative stress in the heart

The effect of oxidative stress on beta-adrenoceptor function in the heart was determined. To this end ventricle membranes, field-stimulated rat left atria and field-stimulated rat right ventricle strips were exposed to 0.1 mM cumene hydroperoxide for 20 min. It was found that oxidative stress increased beta-adrenoceptor number and reduced c-AMP formation in the ventricle membranes. In the rat left atria and rat right ventricle strips the efficacy of beta-adrenoceptor agonists was reduced to approximately 30% of the control value, whereas maximal beta-adrenoceptor-mediated response was reduced to 50%. Using membranes from control atria and from atria exposed to oxidative stress, it was found that oxidative stress had no effect on beta-adrenoceptor density, nor on the affinity of (-)isoproterenol for the receptor. c-AMP production in membranes prepared from atria exposed to oxidative stress was reduced to approximately 30% of the c-AMP production in membranes prepared of control atria. In addition, it was found that the shape of the function that transduces the stimulus which is generated by receptor activation into an effect, is not altered by oxidative stress. It was concluded that the reduction of the efficacy of beta-adrenoceptor agonists by oxidative stress is probably caused by the reduction of c-AMP formation. Because the efficacy of forskolin and of dibutyryl c-AMP was not affected by oxidative stress, the reduced c-AMP formation is probably caused by an impaired coupling between the receptor and adenylate cyclase. The reduction of maximal beta-adrenoceptor-mediated response might be the result of cytotoxic aldehydes that are produced during oxidative stress. In ischemia, catecholamine release and subsequent beta-adrenoceptor hyperstimulation lead to cardiotoxicity. As shown in the present study, oxidative stress reduces beta-adrenoceptor function. This might represent a protective physiological feedback mechanism that protects the heart against excessive beta-adrenoceptor stimulation.     

Percutaneous closure of a coronary fistula between the right coronary artery to the left atrium

We describe a case of a congenital coronary artery fistula of the right coronary artery draining into the left atrium in an eight-year-old boy. The initial diagnosis was made after the detection of a continuous cardiac murmur at the age of six years. Transthoracic echocardiography showed the right coronaric ostium dilatation, the site of drainage in the left atrium and left ventricle volume overload. Catheterization confirmed the diagnosis. The patient underwent percutaneous closure by PDA occluder device. Immediate post-closure angiograms showed complete occlusion of the fistula. The patient showed transient ischemic changes on ECG associated to an increase of plasmatic levels of the cardiac enzyme. ECG and cardiac enzyme were normal one week after the procedure.     

血管内皮生长因子对猪心肌侧枝血管生成的作用

为检测血管内皮生长因子165（VEGF165)能否促进冠状动脉侧枝血管形成,实验在成功制作小型猪慢性心肌缺血模型后,将以复制缺陷复组腺病毒为载体的人VEGF165互补脱氧核糖核酸[(cDNA)Ad-VEGF165]直接注入左回旋支（LCX）分布的缺血心肌内,以心电图门控单光子发射计算机断层摄影和离体太动脉造影检测冠状动脉侧枝形成,心肌灌注和功能变化,结果显示,与对照组和自身给预Ad-VEGF165前比较,给予Ad-VEGF165四周后心肌缺血面积（P＜0．01）和最大缺血程度（P＜0．01）明显减小,左心室射血分数（P＜0．01）TCX区局部心室壁运动（P＜0．05）明显改善,治疗组侧枝血管生成明显多于对照组（P＜0．05）,表明Ad-VEGF165能诱导心肌侧肢血管形成并改善心肌灌注与运动功能。     

Effect of hypoxic hypoxia on taurine concentrations in ventricles of mouse hearts

The effects of hypoxic hypoxia on the concentration of taurine in right ventricles was studied in the hearts of male CF1 mice caged individually and maintained for 16 hr per day in a hypobaric chamber evacuated to an air pressure of 307 mm Hg. After 23 days hearts were excised and right and left ventricles were separated and lyophilized. Hematocrits in chamber animals were 77-82%, compared to 45-49% for control mice. Mean weights of right ventricles of animals from the chamber were 11.2 +/- 0.9, compared to control values of 7.0 +/- 0.4, mg dry weight. The mean dry weights of left ventricles in both groups of animals were the same. There were no significant differences in the nmoles taurine per mg day tissue in either heart chamber, with mean values +/- S.E.M. of 124.0 +/- 4.6 and 135.0 +/- 4.5 in right ventricles and 128.0 +/- 4.3 and 110.9 +/- 15.3 in left ventricles of experimental and control animals respectively. Thus, hypertrophy which results from hypoxia is not accompanied by increased concentrations of taurine in right ventricles.     

Sandostatin inhibits development of medial proliferation of pulmonary arteries in a rat model of pulmonary hypertension

We investigated the effects of subcutaneous administration of 50 and 100 μg/kg/day of sandostatin on monocrotaline-induced medial proliferation of pulmonary arteries and right ventricular overload in rats. In a dosage of 100 μg/kg/day, sandostatin significantly reduced right ventricular systolic pressure, the mass ratio of the right ventricular free wall to the left ventricle, the right ventricular wall thickness, the right ventricular myofiber diameter, the percent medial pulmonary artery thickness, the percent area of smooth muscle cell, and proliferating cell nuclear antigen activity. Our results suggest that sandostatin inhibits development of medial proliferation of pulmonary arteries and right ventricular overload in a dosage of 100 μg/kg/day.     

Parasympathetic control of the heart. I. An interventriculo-septal ganglion is the major source of the vagal intracardiac innervation of the ventricles.

The locations, projections, and functions of the intracardiac ganglia are incompletely understood. Immunocytochemical labeling with the general neuronal marker protein gene product 9.5 (PGP 9.5) was used to determine the distribution of intracardiac neurons throughout the cat atria and ventricles. Fluorescence microscopy was used to determine the number of neurons within these ganglia. There are eight regions of the cat heart that contain intracardiac ganglia. The numbers of neurons found within these intracardiac ganglia vary dramatically. The total number of neurons found in the heart (6,274 +/- 1,061) is almost evenly divided between the atria and the ventricles. The largest ganglion is found in the interventricular septum (IVS). Retrogradely labeled fluorescent tracer studies indicated that the vagal intracardiac innervation of the anterior surface of the right ventricle originates predominantly in the IVS ganglion. A cranioventricular (CV) ganglion was retrogradely labeled from the anterior surface of the left ventricle but not from the anterior surface of the right ventricle. These new neuroanatomic data support the prior physiological hypothesis that the CV ganglion in the cat exerts a negative inotropic effect on the left ventricle. A total of three separate intracardiac ganglia innervate the left ventricle, i.e., the CV, IVS, and a second left ventricular (LV2) ganglion. However, the IVS ganglion provides the major source of innervation to both the left and right ventricles. This dual innervation pattern may help to coordinate or segregate vagal effects on left and right ventricular performance.     

Implantation of the Right and Left Internal Mammary Arteries with Epicardiectomy and Free Omental Graft: A Preliminary Experimental Report

In animal experiments the right internal mammary artery was implanted into the outflow tract of the right ventricle during performance of left mammary artery implantation with epicardiectomy and free omental graft. The effect of double mammary artery implantation operation was tested by triple coronary artery ameroid constriction in 24 animals. In 20 animals studied both implanted arteries remained open and had commenced to bud and branch at the time of examination. The double implant operation is still an experimental procedure.     

Distribution and origin of substance P and neuropeptide Y-immunoreactive nerves in the guinea-pig heart

Summary The localization and origin of substance P (SP)-, neuropeptide Y (NPY)-, and noradrenaline/tyrosine hydroxylase (NA/TH)-immunoreactive (IR) nerves in the guinea-pig heart were investigated by means of immunohistochemistry; quantitative analysis was performed by radioimmunoassay (NPY) and high performance liquid chromatography (NA). Both untreated animals and animals subjected to stellatectomy, combined stellatectomy and local capsaicin pretreatment of the vagal nerves or systemic application of capsaicin were studied. A dense network of SP-IR nerves was observed in the right atrium in different locations: (1) around local cardiac ganglion cells, (2) close to blood vessels, (3) within the myocardium, and (4) close to and within peri and endocardium.A moderately dense SP-innervation, mainly related to blood vessels, was found in the ventricles. Very dense networks of NPY and TH-IR nerve fibers with an overlapping distributional pattern around blood vessels and in the myocardium were seen in both the atria and the ventricles. In addition, some cell bodies in local cardiac ganglia were NPY-IR. Bilateral stellatectomy resulted in a reduction of SP-IR in the right atrium (55% of control), which was more pronounced after additional capsaicin pretreatment of the vagal nerves (44% of control).In the left ventricle no significant depletion of SP-IR was seen by either stellatectomy or combined stellatectomy and capsaicin treatment of the vagal nerves. It was not possible to establish any defined target areas within the heart for vagal or spinal SP-IR afferents by use of immunohistochemical methods. Systemic capsaicin treatment caused a total loss of SP-IR nerves in the heart. After bilateral stellatectomy the levels of NPY-IR and NA were reduced to about 10% of control in both the right atrium and left ventricle. In accordance, NPY and TH-IR nerves were also almost totally absent in the heart after bilateral stellatectomy.     

金钱豹和猪獾冠状动脉的解剖

为了阐明金钱豹(Panthera pardus)和猪獾(Arctonyx collaris)心冠状动脉的分支分布特征及血供情况,为心脏生物学及动物学研究提供结构基础资料,利用血管铸型和组织透明方法观察研究了金钱豹与猪獾心左、右冠状动脉的分支分布.结果表明,金钱豹和猪獾的心均由左右冠状动脉营养.金钱豹左冠状动脉分为室间隔支、前降支和旋支.前降支又分出左室上支、左室中支和左室下支.右冠状动脉沿途分出右室前支、右室后下支和右室后上支.猪獾左冠状动脉分为前降支和旋支.前降支又分出室间隔支和左室前支,旋支又分出左缘支和左室后支.其右冠状动脉沿途分出右室前支、右缘支和右室后支.金钱豹和猪獾心的室间隔均由发自左冠状动脉的独立的室间隔支营养,二者左右冠状动脉在膈壁的分布属于均衡型.     

Myoglobin content and citrate synthase activity in different parts of the normal human heart

Myoglobin (Mb) content and citrate synthase (CS) activity were determined in myocardial samples from nine human brain-dead organ donors with normal hearts. Six regions of each heart were analyzed: right and left atria, right ventricle, left ventricular subepicardium, subendocardium, and anterior papillary muscle. The Mb content was similar, whereas the CS activity was higher in the left than in the right heart at both atrial and ventricular levels. Mb content and CS activity were higher in ventricles than in atria. The subendocardial layer and papillary muscle of the left ventricle had a higher Mb content than the subepicardial layer, whereas CS activity was similar in these three locations. The results suggested a closer relationship between CS activity (oxidative potential) and work load than between Mb content and work load. Mb content may, instead, be related to intramuscular oxygen tension (PO2) on the basis of a comparison between our Mb data and those of others on regional variations in myocardial PO2.     

Effect of ethanol on myocardial infarct size in a canine model of coronary artery occlusion-reperfusion

This study was conducted to determine if elevated blood alcohol prior to acute coronary artery occlusion affects myocardial infarct size in an in vivo canine model. Seven pentobarbital anesthetized open-chest dogs received 10 min Iv infusion of ethanol (0.08 g/kg/min). Ten min after ethanol, the left anterior descending coronary artery (LAD) was occluded distal to its first major branch for 60 min. The LAD was then reperfused for 5 h. Following electrically induced ventricular fibrillation, the area at risk of infarction was delineated with dye. The area of infarction was identified by staining with triphenyl tetrazolium chloride. Eleven untreated control experiments were also conducted. Mean blood ethanol concentration was 155 ± 26 mg/dl just prior to LAD occlusion and 47 ± 3 mg/dl after 4 h reperfusion. Ethanol infusion had no effect on systemic hemodynamic variables during ischemia. In ethanol treated animals, the area at risk was 19.7 ± 3.0% of the left ventricle, and the infarct size was 20.9 ± 4.8% of the area at risk. In control experiments, the area at risk was 23.0 ± 4.1% of the left ventricle (p > 0.05), and the infarct size was 21.6 ± 3.8% of the area at risk (p > 0.05). Collateral blood flow to ischemic region did not differ between the two groups, and the relationships between infarct size and collateral flow were similar for control and untreated hearts. Acute ethanol exposure prior to coronary artery occlusion and subsequent reperfusion does not affect myocardial infarct size in the heart of the anesthetized dog.     

Comparative stereology of mouse atria

The left and right atria of the mouse were compared to each other and to the mouse left ventricle using stereologic techniques. The volume fraction (V_v) and surface area per unit cell volume (S_v) of the interior junctional sarcoplasmic reticulum (IJSR), total JSR and extended JSR were greater in the left atrium than in right. The V_v and S_v of the free SR, transverse tubules, and mitochondria were similar in the two atria. It is suggested that the differences in junctional sarcoplasmic reticulum between the atria can be accounted for by a difference in distribution of two types of cells whose anatomy is analogous to working and conducting fibers in the ventricle. The S_v and V_v of the transverse tubules, mitochondria, and all the components of the sarcoplasmic reticulum except for the free SR were greater in the left ventricle than in either atrium. The greater calcium content and sensitivity to extracellular calcium of the atria may explain the greater volume of free SR in the atria as compared to the left ventricle. The S_v of the plasmalemma of the atria and of the S_v of the plasmalemma of the transverse tubules of the left ventricles supports the suggestion of others that there is a constant ratio of surface area to cell volume in cardiac cells.