Ventricle Papillary Muscle Research Articles

Age-related fibromuscular dysplasia in the human left ventricle papillary muscles arteries.

We describe histologically cases of patients between 31 and 60years of age who had fibromuscular dysplasia (FMD) in the tunica media (TM) of the left ventricle papillary muscles (PM) arteries. We also compared them with our previous findings in subjects younger than 30years of age. We examined histologically samples taken from the tip of the anterior PM of the left ventricle in 200 healthy male hearts. In 33 cases (16.5%), FMD was in the TM. We divided these cases into three subgroups (A, B, C) based on the degree of replacement of smooth muscle cells by fibrous tissue, and thus identified 17, 11 and 5 cases, respectively. Until the age of 41, the typical lesions were often localized within the TM. Beyond that age, the fibrous tissue increased in the TM wall and in the surrounding area of the vessels, causing dysfunction of the PM. Degenerative lesions, as well as inflammatory infiltration, were found after the age of 53. The findings of this study will be useful to cardiologists and cardiac surgeons, in pointing out that, after the age of 44years old, some PM and their supporting valves may present a degree of dysfunction.

Effects of endothelin and nitric oxide on cardiac muscle functions in experimental septic shock model.

We aimed to investigate the possible roles of nitric oxide (NO) and endothelin on the changes of cardiac muscle function in both hyper- and hypodynamic septic shock periods. Cecal ligation and puncture was performed in 50 Wistar albino rats to induce septic shock. Changes in atrium and right ventricle papillary muscle contractions, atrium beat rate, adrenergic and cholinergic responses in these tissues were evaluated in vitro. Atrium beat rate increased in hypodynamic period (p < 0.001) that was reversed by bosentan (p < 0.001) and N(G)-nitro-L-arginine methylester (L-NAME; p < 0.05). Atrium contractions decreased in both hyper- and hypodynamic periods (p < 0.001) that were partially ameliorated by bosentan in both periods (p < 0.01) and only in hypodynamic period by L-NAME (p < 0.001). L-NAME increased papillary muscle contractions in both periods (p < 0.01), but bosentan increased it only in hyperdynamic period (p < 0.01). Bosentan and L-NAME increased potency of isoproterenol on atrium beat rate in both periods and increased carbachol potency on atrium beat rate and atrium contraction amplitude only in hypodynamic period. Bosentan increased atrium contraction response to isoproterenol in hypodynamic period (p < 0.05). Papillary muscle contraction response to isoproterenol increased in hypodynamic period (p < 0.05). L-NAME increased papillary muscle contraction response to carbachol in both periods (p < 0.01, p < 0.05, respectively). These results show that NO and endothelin may play a role in positive inotropic and negative chronotropic effects for atrium in septic shock. Bosentan and L-NAME may change potency and efficacy of isoproterenol and carbachol via upregulation of adrenergic and cholinergic receptors and/or through post receptor factors.

Regulation of Cardiomyocyte T-Tubule Organization and Density by Ventricular Wall Stress

During heart failure development, t-tubules become disorganized which disrupts Ca2+ homeostasis and weakens contraction of the heart. The mechanisms controlling t-tubular structure in the normal and failing heart remain unknown, but accumulating data suggest that ventricular workload may be an important regulator. In Wistar rats which had developed heart failure 6 weeks following myocardial infarction, we observed that marked t-tubule disruption occurred preferentially in regions of the heart that are proximal to the infarct site, while t-tubule density was normal in distal locations. In vivo imaging by MRI has revealed near-isometric contraction in this proximal zone, with dramatically elevated wall stress due to local thinning of the ventricular wall and elevated diastolic blood pressure. To directly investigate whether elevated wall stress triggers t-tubule disruption, we developed an in vitro model for culturing isolated rat left ventricle papillary muscles in a myobath system (0.5 Hz stimulation, 48 hours). Muscles were subjected to varying amounts of stretch to approximate wall stress values observed in vivo. Muscles exposed to low diastolic wall stress similar to that observed in sham-operated hearts (3.5-4.5 mN/mm2), exhibited well-maintained t-tubule organization during culture (t-tubule fraction of cross-sectional area = 0.174 ± SE 0.007). Exposure to high wall stress (10-15 mN/mm2) triggered marked t-tubule loss during culture (t-tubule fraction = 0.079 ± SE 0.012), and reduction in both peak and between-peak power in Fast-Fourier Transform analyses. In addition, cell size was observed to be markedly increased by elevated wall stress in comparison with muscles that were exposed to low wall stress (cross-sectional area = 1022.71 ± SE 48.00 µm2 vs 564.41 ± SE 25.34 µm2, P < 0.05). Thus, our data indicate that wall stress is an important regulator of both cellular geometry and t-tubular structure.

Abstract 155: Cardiac Function And Calcium Handling in Obesity-Resistant rats

Experimental studies have demonstrated that obesity induced by different types of high-fat and/or high-energy diets also lead to myocardial dysfunction. Nevertheless, few studies have evaluated the myocardial function in obesity-resistant rats. Moreover, the mechanisms underlying the participation of calcium (Ca 2+ ) handling on cardiac function in this model remain unknown. The aim of this study was to investigate in rodent model of obesity-resistant. In addition, as obesity-resistant group is fed a high-fat diet but did not become obese, this study tested whether obesity-resistant model develops cardiac abnormalities and impairment of calcium handling as obesity-prone. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable unsaturated high-fat diets (Ob) for 15 weeks. After experimental protocol, Ob rats consuming the unsaturated high-fat diets were ranked based on adiposity index. Rats on the unsaturated high-fat diets exhibiting the greatest adiposity index were referred to as OP, whereas those exhibiting the lowest adiposity index were referred to as OR. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. After 15 weeks, final body weight, total body fat, adiposity index, triglycerides levels and heart weight were significantly greater in OP rats than C and OR rats, however, there was no change in systolic blood pressure between groups. The C, OP and OR muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus was compromised in OP rats. In conclusion, obesity-resistant model by unsaturated high-fat diet, after 15 weeks, does not display nutritional and metabolic characteristics of obesity-prone. Furthermore, obesity-resistant does not promote cardiac abnormalities and impairment of calcium handling visualized in obesity-prone.

Carvedilol Prevents Ovariectomy-Induced Myocardial Contractile Dysfunction in Female Rat

Carvedilol has beneficial effects on cardiac function in patients with heart failure but its effect on ovariectomy-induced myocardial contractile dysfunction remains unclear. Estrogen deficiency induces myocardial contractile dysfunction and increases cardiovascular disease risk in postmenopausal women. Our aim was to investigate whether carvedilol, a beta receptor blocker, would prevent ovariectomy-induced myocardial contractile dysfunction. Female rats (8 weeks old) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with carvedilol (OVX+CAR, 20 mg/kg), placebo (OVX) and SHAM for 58 days. Left ventricle papillary muscle was mounted for isometric tension recordings. The inotropic response to Ca2+ (0.62 to 3.75 mM) and isoproterenol (Iso 10−8 to 10−2 M) were assessed. Expression of calcium handling proteins was measured by western blot analysis. Carvedilol treatment in the OVX animals: prevented weight gain and slight hypertrophy, restored the reduced positive inotropic responses to Ca2+ and isoproterenol, prevented the reduction in SERCA2a expression, abolished the increase in superoxide anion production, normalized the increase in p22phox expression, and decreased serum angiotensin converting enzyme (ACE) activity. This study demonstrated that myocardial contractile dysfunction and SERCA2a down regulation were prevented by carvedilol treatment. Superoxide anion production and NADPH oxidase seem to be involved in this response.

Vascular Remodeling–Associated Hypertension Leads to Left Ventricular Hypertrophy and Contractile Dysfunction in Profilin-1 Transgenic Mice

Hypertension is a major health problem and a main risk factor for cardiovascular diseases. We have shown that overexpression of profilin-1 in blood vessels of transgenic mice generates mechanical tone and led to vascular remodeling/hypertension. However, little is known whether cardiac contractile performance in these mice is compromised. We investigated the in vivo contractile function and in vitro contractile performance using isolated papillary muscles from both right ventricle and left ventricle of profilin-1 mice at older age. Our results showed mild left ventricular hypertrophy and moderate systolic dysfunction in profilin-1 mice as evident by increased heart/body weight ratio and echocardiography analysis. Under near physiological conditions, right ventricle papillary muscles of profilin-1 mice maintained their peak isometric active developed tension, and the rate of force development over the entire frequency range of 4-14 Hz. Positive inotropic responses to increasing Ca and β-adrenergic stimulation were also maintained. Conversely, left ventricular papillary muscles of profilin-1 mice exhibited depressed peak isometric, peak isometric active developed tension and rate of force development, and depressed positive inotropic responses to increasing Ca and β-adrenergic stimulation. We here provide functional evidence that a significant contractile dysfunction in profilin-1 mice exists. Targeting vascular profilin-1 signaling could represent a promising therapeutic approach in hypertensive patients.

Cardiac remodeling in rats with renal failure shows interventricular differences

Chronic renal failure (CRF) is associated with an increased incidence of cardiovascular diseases. Intensive research revealed a number of alterations in the heart during CRF; however, possible interventricular differences in CRF-induced cardiac remodeling have so far not been addressed. CRF was induced by two-stage surgical 5/6 nephrectomy (NX) in male Wistar rats. Cellular hypertrophy was quantified using immunohistological morphometric analysis. Contraction force and membrane potential were recorded in left and right ventricle papillary muscles with an isometric force transducer and high-resistance glass microelectrodes. Hypertrophy was present in the left ventricle (LV) of NX animals, but not in the right ventricle (RV) of NX animals, as documented by both ventricle/body weight ratios and cellular morphometric analysis of the cross-sectional area of myocytes. The contraction force was reduced in the LV of NX animals but increased in the RV of NX animals compared with sham-operated rats. Rest potentiation of contraction force was relatively more pronounced in the LV of NX rats. Fifty percent substitution of extracellular sodium with lithium significantly increased the contraction force only in the LV of NX animals. Action potential durations were shortened in both ventricles of CRF animals. Cardiac structural and contractile remodeling in CRF shows significant interventricular differences. CRF induces hypertrophy of the LV but not of the RV. LV hypertrophy was associated with a reduction of contraction force, whereas in the RV, the contraction force was enhanced. Partial recovery of contractile function of the LV by rest potentiation or lithium substitution indicates a role of the Na(+)/Ca(2+) exchanger in this phenomenon.

Myocardial oxidative stress in patients with active infective endocarditis

BackgroundInfective endocarditis (IE) induces the rise of pro-inflammatory cytokines. Some of them can stimulate oxidants production in myocardium with subsequent peroxidative damage to various biomolecules. We compared indices of oxidative stress: H2O2, thiobarbituric acid-reactive substances (TBARs), thiols in myocardium specimens between patients with active IE and those with valvular heart disease (VHD) of rheumatic etiology who underwent surgical valve replacement. Methods17 left ventricle papillary muscle specimens and 28 specimens of auricle of the right heart were collected from 45IE patients, and 16 papillary muscle and 12 auricle specimens from 28 VHD patients, respectively. Patients groups had similar NYHA functional class and majority of echocardiographic indices of heart morphology. H2O2 and TBARs were determined fluorometrically in myocardium homogenates whereas thiols with photometric method. Between and within groups comparisons and mutual correlations between variables were analyzed. ResultsH2O2 generation from all myocardium specimens and auricles was 2.14- and 2.59- times higher (p<0.001) in IE patients than in VHD group. Auricles had the highest H2O2 levels within IE group. TBARs were 10-times higher (p<0.05) in IE when compared to VHD group in auricles and papillary muscles. Thiols did not differ between groups.H2O2 positively correlated with TBARs and negatively with thiols in all IE myocardium specimens (r=0.31 and r=−0.46, p<0.05) and auricles (r=0.58 and r=−0.67, p<0.05), respectively. No such associations were noted in VHD specimens. ConclusionsActive IE induces enhanced myocardial production of H2O2 and formation of TBARs which proves occurrence of oxidative stress in the heart.

Značaj ranog prepoznavanja i pravilnog lečenja infarkta desne komore

There is significantly higher mortality rate in inferior infarctions associated with right ventricular infarctions, about 30 %, compared with 6 % in cases without right ventricular infarctions. The causes of the increased mortality rate are complications occurring in over 50 % of patients. The most frequent ones are conduction disturbances such as 2-nd and 3-rd degree AV block, atrial fibrillation and interventricular conduction disturbances. Also, rupture of the right ventricle free wall, interventricular septum and right ventricle papillary muscles are frequent. In this paper, a case of acute inferoposterior infarction with right ventricular infarction has been reported, with patient developing conduction complications, namely transient complete AV block, frequent ventricular extrasystoles and epistenocardiac pericarditis.

Disfunção miocárdica e alterações no trânsito de cálcio intracelular em ratos obesos

Several mechanisms have been proposed to contribute to cardiac dysfunction in obesity models, such as alterations in calcium (Ca²⁺) handling proteins and β-adrenergic receptors. Nevertheless, the role of these factors in the development of myocardial dysfunction induced by obesity is still not clear. The purpose of this study was to investigate whether obesity induced by hypercaloric diets results in cardiac dysfunction. Furthermore, it was evaluated whether this functional abnormality in obese rats is related to abnormal Ca²⁺ handling and the β-adrenoceptor system. Male 30-day-old Wistar rats were fed with standard food (C) and a cycle of five hypercaloric diets (Ob) for 15 weeks. Obesity was defined as increases in body fat percentage in rats. Cardiac function was evaluated by isolated analysis of the left ventricle papillary muscle under basal conditions and after inotropic and lusitropic maneuvers. Compared with the control group, the obese rats had increased body fat and glucose intolerance. The muscles of obese rats developed similar baseline data, but the myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca²⁺ were compromised. There were no changes in cardiac function between groups after β-adrenergic stimulation. Obesity promotes cardiac dysfunction related to changes in intracellular Ca²⁺ handling. This functional damage is probably caused by reduced cardiac sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2) activation via Ca²⁺ calmodulin kinase.

Modeling vectorcardiograms based on left ventricle papillary muscle position

Background Vectorcardiographic QRS loops illustrate the electrical activation of the left ventricle (LV) in 3-dimensional space; however, the individual variability in these loops is not well understood. The left bundle-branch fan distributes the initial activation to the LV and has been shown to distribute its fascicles between the LV papillary muscles. Computer models of LV activation using papillary muscle as the initial electrical activation points accurately predict QRS duration and frontal plane axis. Methods Twelve healthy adults received standard 12-lead electrocardiograms and 1.5-T cardiac magnetic resonance imaging. A software developed by ECG-TECH Corp (Huntington Station, NY) generated 3-dimensional QRS vector loops for each subject. Short- and long-axis papillary muscle positions were measured for each subject using cardiac magnetic resonance images. A theoretical plane equidistant from the endocardial origins of each papillary muscle was constructed. Vectors perpendicular to the QRS vector loop and the theoretical plane termed the plane identifier were used for comparison. Spearman rank correlation was used to compare the azimuth and elevation of the plane identifiers of the QRS vector loop and the theoretical plane. Results No correlation was found between the azimuth or elevation of the theoretical plane and the QRS vector loops with Spearman rank correlation coefficients of ρ = 0.11 ( P = .71) and ρ = 0.22 ( P = .49), respectively. Subgroup analysis by QRS vector loop morphology (planar vs nonplanar, narrow vs wide) also demonstrated no correlation. Conclusions Modeling the activation of the LV based on papillary muscle position alone may be overly simplistic. Better understanding of what other factors contribute to individual variation in LV activation will help develop a more useful theoretical model.

Involvement of L‐type calcium channel and serca2a in myocardial dysfunction induced by obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca(2+) ) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca(2+) channels and sarcoplasmic reticulum (SR) Ca(2+) -ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca(2+) channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca(2+) channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca(2+) was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca(2+) channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca(2+) channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca(2+) protein levels.

Myocardial contractility is preserved early but reduced late after ovariectomy in young female rats

BackgroundOvarian sex hormones (OSHs) are implicated in cardiovascular function. It has been shown that OSHs play an important role in the long term regulation of cardiac sarcoplasmic reticulum (SR) function and contractility, although early effects of OSHs deprivation on myocardial contractility have not yet been determined. This study evaluated the early and late effects of OSHs deficiency on left ventricular contractility in rats after ovariectomy.MethodsYoung female Wistar rats were divided into 3 groups (n = 9-15): sham operated (Sham), ovariectomized (Ovx) and Ovx treated with estradiol (1 mg/kg, i.m., once a week) (Ovx+E2). After 7, 15, 30 and 60 days post Ovx, left ventricle papillary muscle was mounted for isometric tension recordings. The inotropic response to Ca2+ (0.62 to 3.75 mM) and isoproterenol (Iso 10-8 to 10-2 M) and contractility changes in response to rate changes (0.25 to 3 Hz) were assessed. Protein expression of SR Ca2+-ATPase (SERCA2a) and phospholamban (PLB) in the heart was also examined.ResultsThe positive inotropic response to Ca2+ and Iso at 7, 15, and 30 days after Ovx was preserved. However, at 60 days, the Ovx group had decreased myocardial contractility which was subsequently restored with E2 replacement. The reduction in SERCA2a and increase in PLB expression observed at 60 days after Ovx were restored with E2 replacement.ConclusionThis study demonstrated that myocardial contractility and expression of key Ca2+ handling proteins were preserved in the early phase and reduced at long-term during OSHs deprivation.

The influence of the neuropeptide galanin on the contractility and the effective refractory period of guinea-pig heart papillary muscle under normoxic and hypoxic conditions.

The aim of this study was to discover the effects of galanin, a neuropeptide comprising 29 amino acids capable of activating inward-rectifier K+ channels (IK1) in cardiomyocytes, on the force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and effective refractory period (ERP) of guinea-pig heart. The influence of galanin on the time-course of hypoxia-induced disturbances in contractility and ERP was also examined. Experiments were performed on the isolated right ventricle papillary muscle of guinea-pig heart. In the concentration range 0.001-0.01 microM, galanin had no significant effect on the measured parameters. At 0.03 and 0.1 microM, galanin exerted a positive inotropic action and prolonged ERP. Further increasing the concentration led to a negative inotropic action and significant shortening of ERP. Although simulated hypoxia induced a significant drop in Fc, +dF/dt and -dF/dt, and a significant shortening of ERP, recovery of all the measured parameters was complete after 10 min reperfusion. In the presence of 0.03 and 0.1 microM galanin the effect of hypoxia on the contractility of papillary muscle was more profound and reperfusion did not result in complete recovery. In contrast, addition of 1 microM galanin to the hypoxic solution significantly protected the muscle and recovery of the tissues during reperfusion was rapid and complete (in 5 min). One can conclude that galanin at lower concentrations induced a positive inotropic action and a prolongation of ERP, but increased the sensitivity of heart muscle to hypoxia. At higher concentrations however, galanin exerted a negative inotropic action but protected the muscle against hypoxia-induced disturbances in contractility.

Losartan and Carvedilol prevent ventricular dysfunction induced by ovariectomy in female rats

Ovarian sex hormones (OSHs) modulates myocardial contractility due to a mechanism involving the intracellular calcium handling. We evaluated the possibility that, at long-term, OSHs could modulates the ventricular contractility dependent on the renin-angiotensin system (RAS) and the noradrenergic receptors. Female Wistar rats were divided into: control (Sham); ooforectomy (OVX); OVX plus Losartan (15 mg/Kg/day i.m., OVX-LOS); OVX plus Carvedilol (20 mg/Kg/dia v.o., OVX-CAR) and OVX plus estrogen (1 mg/Kg i.m., once a week). After 60 days the inotropic responses to Ca2+ and to isoproterenol were assessed using isolated left ventricle papillary muscle. The cardiac protein expression of SERCA2a and phospholamban was determined. The body weight gain in the OVX group was reverted by estrogen and losartan treatment (Sham: 257±5; OVX:305±9*; OVX-LOS:277±3#; OVX-CAR:295±4; OVX-E2:251±9# g *#p<0.05). The reduced positive inotropic response to Ca2+ and Isoproterenol was restored by estrogen, losartan and carvedilol replacement (Ca2+=3.75 mM: Sham:650±42; OVX:388±35*; OVX-LOS:636±61#; OVX-CAR:591±51#; OVX-E2:593±76# g/g, *#p<0.05 and Isoproterenol=10-3 M:Sham:598±41; OVX:311±32*; OVX-LOS:586±57#; OVX-CAR:545±66#; OVX-OVX-Estrogen:574±45# g/g, *#p<0.05). The reduction in SERCA2a and the increase in phospholamban protein expression in the OVX group were restored by all treatment.

Cardiac remodeling in a rat model of diet-induced obesity

The mechanisms by which diet-induced obesity cause remodeling and cardiac dysfunction are still unknown. Interstitial collagen and myocardial ultrastructure are important in the development of left ventricular hypertrophy, and are essential to the adaptive and maladaptive changes associated with obesity. Thus, the accumulation of collagen and ultrastructural damage may contribute to cardiac dysfunction in obesity. The purpose of the present study was to investigate cardiac function in a rat model of diet-induced obesity and to test the hypothesis that cardiac dysfunction induced by obesity is related to myocardial collagen deposition and ultrastructural damage. Thirty-day-old male Wistar rats were fed standard (control [C]) and hypercaloric diets (obese [Ob]) for 15 weeks. Cardiac function was evaluated by echocardiogram and isolated left ventricle papillary muscle. Cardiac morphology was assessed by histology and electron microscopy. Compared with C rats, Ob rats had increased body fat, systolic blood pressure and area under the curve for glucose, leptin and insulin plasma concentrations. Echocardiographic indexes indicated that Ob rats had increased left ventricular mass, increased systolic stress and depressed systolic function. Analysis of the isolated papillary muscle was consistent with higher myocardial stiffness in Ob compared with C rats. The Ob rats had an increase in myocardial collagen and marked ultrastructural changes compared with C rats. Obesity promotes pathological cardiac remodeling with systolic dysfunction and an increase in myocardial stiffness, which, in turn, is probably related to afterload elevation and cardiac fibrosis. Obesity also causes damage to myocardial ultrastructure, but its effect on myocardial function needs to be further clarified.

Fatal diquat intoxication

Since the introduction of diquat in agriculture practice in 1960's, about 40 cases of poisoning have been described in detail in medical literature. We presented two cases. A case one, a 35-year-old, previously healthy, woman ingested 14% diquat solution. The poisoning had fulminant course, consisted of severe stomachache, vomiting, cardiocirculatory shock, respiratory failure and cardiac arrest 20 hours post-ingestion. Autopsy revealed myocardial infarction, bronchopneumonia and incipient renal damage. A case two, a 64-year-old man developed severe gastroenteritis, corrosive lesions of mucosal surfaces, acute renal injury, arrhythmias, brain stem infarction and bronchopneumonia. The diagnosis of diquat poisoning was made retrospectively upon the clinical picture and identification of pesticides he had been exposed to. The patient died 18 days post-exposure. The most prominent findings on autopsy were pontine hemorrhage and infarction, bronchopneumonia, left ventricle papillary muscle infarction and renal tubular damage. Cardiocirculatory disturbances led to fatal complications, the heart and brain infarction. We pointed out the heart as one of the most severely affected organs in diquat poisoning.

Protease-Activated Receptor-1 Mediates Thrombin-Induced Persistent Sodium Current in Human Cardiomyocytes

After the thrombus formation in cardiac cavities or coronaries, the serine protease thrombin is produced and can therefore reach the myocardial tissue by the active process of extravasation and binds to the G protein-coupled protease-activated receptor-1 (PAR1) expressed in human myocardium. The role of PAR1 was investigated in the thrombin effect on sodium current (I(Na)). I(Na) was recorded in freshly isolated human atrial myocytes by the whole-cell patch-clamp method. Action potentials (AP) were recorded in guinea pig ventricular tissue by the conventional glass microelectrode technique. Thrombin-activated PAR1 induced a tetrodotoxin-blocked persistent sodium current, I(NaP), in a concentration-dependent manner with an apparent EC(50) of 28 U/ml. The PAR1 agonist peptide SFLLR-NH(2) (50 microM) was able to mimic PAR1-thrombin action, whereas PAR1 antagonists N(3)-cyclopropyl-7-((4-(1-methylethyl)-phenyl)methyl)-7H-pyrrolo(3,2-f)quinazoline-1,3-diamine (SCH 203099; 10 microM) and 1-(3,5-di-tert-butyl-4-hydroxy-phenyl)-2-[3-(3-ethyl-3-hydroxy-pentyl)-2-imino-2,3-dihydro-imidazol-1-yl]-ethanone (ER 112787) (1 microM), completely inhibited it. The activated PAR1 involves the calcium-independent phospholipase-A(2) signaling pathway because two inhibitors of this cascade, bromoenol lactone (50 microM) and haloenol lactone suicide substrate (50 microM), block PAR1-thrombin-induced I(NaP).Asa consequence of I(NaP) activation, in guinea pig right ventricle papillary muscle, action potential duration (APD) were significantly increased by 20% and 15% under the respective action of 32 U/ml thrombin and 50 microM SFLLR-NH(2), and these increases in APD were prevented by 1 microM tetrodotoxin or markedly reduced by application of 1 microM SCH 203099 or ER 112787. Thrombin, through PAR1 activation, increases persistent component of the Na(+) current resulting in an uncontrolled sodium influx into the cardiomyocyte, which can contribute to cellular injuries observed during cardiac ischemia.

Depressed cardiac contractility and its postnatal development in rats after chemical sympathectomy

The contribution of the sympathetic innervation to the postnatal development of cardiac contractility remains unclear. In this study, the postnatal maturation of cardiac contractility was compared in control rats and rats after chemical sympathectomy. The chemical sympathectomy was induced by administration of 6-hydroxydopamine to newborn rats. At days 20, 40 and 60 of postnatal life, the contractile parameters and concentrations of sympathetic neurotransmitters were measured in both right and left ventricles. In rats with chemical sympathectomy, concentrations of norepinephrine were reduced almost completely in both ventricles at all time points. The contractility of the left ventricle papillary muscles was substantially decreased at all time points. In contrast, the contractility of the right ventricle papillary muscles was decreased only transiently, showing a recovery at day 60 regardless of the permanently decreased concentration of norepinephrine. The concentration of neuropeptide Y, another neurotransmitter present in sympathetic nerves, showed the same developmental trend as contractility: permanent reduction in the left ventricle, transient reduction with a recovery at day 60 in the right ventricle. The data indicate that the sympathetic nervous system plays an important role in the postnatal development of cardiac contractility and neuropeptide Y may contribute to this effect.

Irrigação dos músculos papilares do ventrículo esquerdo do coração de caninos (Canis familiaris, L. 1758)

A irrigação dos músculos papilares tem informações incompletas sobre a distribuição dos vasos arteriais. Objetivando estabelecer a origem destas artérias e sua distribuição nos músculos papilares do ventrículo esquerdo, utilizamos 30 corações de cães adultos, machos e fêmeas de raça não definida e de várias idades. Após o óbito, o coração foi removido, lavado em água corrente e em seguida injetado através do óstio da artéria coronária esquerda com uma solução de acetato de vinil corado, neoprene látex 650 corado ou gelatina a 10%. Os músculos papilares em todas as técnicas utilizadas foram fixados com solução de formol a 10%. A dissecação foi realizada de forma acelerada com o uso de solução de ácido sulfúrico a 40%. Para realização das radiografias utilizamos injeção de mercúrio o que auxiliou a montagem dos esquemas da vascularização estudada. Utilizamos a técnica de diafanização de Spalteholz para melhor visualizar a irrigação cardíaca. Evidenciamos que os músculos papilares subauricular e subatrial são irrigados pelos ramos da artéria coronária esquerda. O subauricular pelos ramos interventricular paraconal e circunflexo e o subatrial predominantemente pelo ramo circunflexo. Os subsegmentos que suprem o subauricular do ramo interventricular paraconal são os ramos: colateral e ventriculares à esquerda; e do ramo circunflexo são os ramos: dorsais à esquerda e intermédio (marginal ventricular esquerdo) e mais raramente o ramo da borda ventricular esquerda (ramo diafragmático). Os subsegmentos do ramo circunflexo que suprem o subatrial são os ramos: intermédio (marginal ventricular esquerdo), da borda ventricular esquerda (ramo diafragmático), ramos dorsais direito e ramo interventricular subsinuoso. Em alguns casos observamos o ramo colateral e o próprio ramo interventricular paraconal atingirem a porção do vértice do subatrial.