Acidaemia reduces cardiac output and left ventricular contractility in conscious lambs

We studied the effects of HCI-induced metabolic acidaemia on cardiac output, contractile function, myocardial blood flow, and myocardial oxygen consumption in nine unanaesthetized newborn lambs. Through a left thoracotomy, catheters were placed in the aorta, left atrium and coronary sinus. A pressure transducer was placed in the left ventricle. Three to four days after surgery, we measured cardiac output, dP/dt, left ventricular end diastolic and aortic mean blood pressures, heart rate, aortic and coronary sinus blood oxygen contents, and left ventricular myocardial blood flow during a control period, during metabolic acidaemia, and after the aortic pH was restored to normal. We calculated systemic vascular resistance, myocardial oxygen consumption and left ventricular work. Acidaemia was associated with reduction in cardiac output, maximal dP/dt, and aortic mean blood pressure. Left ventricular end diastolic pressure and systemic vascular resistance increased, and heart rate did not change significantly. The reduction in myocardial blood flow and oxygen consumption was accompanied by fall in cardiac work. Cardiac output returned to control levels after the pH had been normalized but maximal dP/dt was incompletely restored. Myocardial blood flow and oxygen consumption increased beyond control levels. This study demonstrates that HCI-induced metabolic acidaemia in conscious newborn lambs is associated with a reduction in cardiac output which could have been mediated by the reduction in contractile function and/or the increase in systemic vascular resistance. The decreases in myocardial blood flow and oxygen consumption appear to reflect diminished cardiac work. The restoration of a normal cardiac output after normalization of the pH appears to have resulted from the increases in heart rate and left ventricular filling pressures in conjunction with an incomplete restoration of contractile function.     

Proteolytic N-terminal truncation of cardiac troponin I enhances ventricular diastolic function

Besides the core structure conserved in all troponin I isoforms, cardiac troponin I (cTnI) has an N-terminal extension that contains phosphorylation sites for protein kinase A under beta-adrenergic regulation. A restricted cleavage of this N-terminal regulatory domain occurs in normal cardiac muscle and is up-regulated during hemodynamic adaptation (Z.-B. Yu, L.-F. Zhang, and J.-P. Jin (2001) J. Biol. Chem. 276, 15753-15760). In the present study, we developed transgenic mice overexpressing the N-terminal truncated cTnI (cTnI-ND) in the heart to examine its biochemical and physiological significance. Ca(2+)-activated actomyosin ATPase activity showed that cTnI-ND myofibrils had lower affinity for Ca(2+) than controls, similar to the effect of isoproterenol treatment. In vivo and isolated working heart experiments revealed that cTnI-ND hearts had a significantly faster rate of relaxation and lower left ventricular end diastolic pressure compared with controls. The higher baseline relaxation rate of cTnI-ND hearts was at a level similar to that of wild type mouse hearts under beta-adrenergic stimulation. The decrease in cardiac output due to lowered preload was significantly smaller for cTnI-ND hearts compared with controls. These findings indicate that removal of the N-terminal extension of cTnI via restricted proteolysis enhances cardiac function by increasing the rate of myocardial relaxation and lowering left ventricular end diastolic pressure to facilitate ventricular filling, thus resulting in better utilization of the Frank-Starling mechanism.     

High-fat diet postinfarction enhances mitochondrial function and does not exacerbate left ventricular dysfunction

Lipid accumulation in nonadipose tissue due to enhanced circulating fatty acids may play a role in the pathophysiology of heart failure, obesity, and diabetes. Accumulation of myocardial lipids and related intermediates, e.g., ceramide, is associated with decreased contractile function, mitochondrial oxidative phosphorylation, and electron transport chain (ETC) complex activities. We tested the hypothesis that the progression of heart failure would be exacerbated by elevated myocardial lipids and an associated ceramide-induced inhibition of mitochondrial oxidative phosphorylation and ETC complex activities. Heart failure (HF) was induced by coronary artery ligation. Rats were then randomly assigned to either a normal (10% kcal from fat; HF, n = 8) or high saturated fat diet (60% kcal from saturated fat; HF + Sat, n = 7). Sham-operated animals (sham; n = 8) were fed a normal diet. Eight weeks postligation, left ventricular (LV) function was assessed by echocardiography and catheterization. Subsarcolemmal and interfibrillar mitochondria were isolated from the LV. Heart failure resulted in impaired LV contractile function [decreased percent fractional shortening and peak rate of LV pressure rise and fall (+/-dP/dt)] and remodeling (increased end-diastolic and end-systolic dimensions) in HF compared with sham. No further progression of LV dysfunction was evident in HF + Sat. Mitochondrial state 3 respiration was increased in HF + Sat compared with HF despite elevated myocardial ceramide. Activities of ETC complexes II and IV were elevated in HF + Sat compared with HF and sham. High saturated fat feeding following coronary artery ligation was associated with increased oxidative phosphorylation and ETC complex activities and did not adversely affect LV contractile function or remodeling, despite elevations in myocardial ceramide.     

Preserved left ventricular structure and function in mice with cardiac sympathetic hyperinnervation

Cardiac-specific overexpression of nerve growth factor (NGF), a neurotrophin, leads to sympathetic hyperinnervation of heart. As a consequence, adverse functional changes that occur after chronically enhanced sympathoadrenergic stimulation of heart might develop in this model. However, NGF also facilitates synaptic transmission and norepinephrine uptake, effects that would be expected to restrain such deleterious outcomes. To test this, we examined 5- to 6-mo-old transgenic (TG) mice that overexpress NGF in heart and their wild-type (WT) littermates using echocardiography, invasive catheterization, histology, and catecholamine assays. In TG mice, hypertrophy of the right ventricle was evident (+67%), but the left ventricle was only mildly affected (+17%). Left ventricular (LV) fractional shortening and fractional area change values as indicated by echocardiography were similar between the two groups. Catheterization experiments revealed that LV +/-dP/dt values were comparable between TG and WT mice and responded similarly upon isoproterenol stimulation, which indicates lack of beta-adrenergic receptor dysfunction. Although norepinephrine levels in TG LV tissue were approximately twofold those of WT tissue, TG plasma levels of the neuronal norepinephrine metabolite dihydroxyphenylglycol were fivefold those of WT plasma. A greater neuronal uptake activity was also observed in TG LV tissue. In conclusion, overexpression of NGF in heart leads to sympathetic hyperinnervation that is not associated with detrimental effects on LV performance and is likely due to concomitantly enhanced norepinephrine neuronal uptake.     

Reservoir and conduit function of right atrium: impact on right ventricular filling and cardiac output

The purpose of this study was to investigate the relationship between right atrial (RA) reservoir and conduit function and to determine how hemodynamic changes influence this relationship and its impact on cardiac output. In 11 open-chest sheep, RA reservoir and conduit function were quantified as RA inflow with the tricuspid valve closed versus open, respectively. Conduit function was separated into early (before A wave) and late (after A wave) components. The effects of inotropic stimulation, partial pulmonary artery occlusion, and pericardiotomy were tested. At baseline with the pericardium intact, reservoir function accounted for 0.56 (SD 0.13) of RA inflow, early conduit for 0.29 (SD 0.07), and late conduit (during RA contraction) for 0.16 (SD 0.11). Inotropic stimulation decreased conduit function and increased reservoir function, but these effects did not reach statistical significance. With partial pulmonary artery occlusion, early conduit function fell to 0.20 (SD 0.11) (P < 0.04), and the conduit-to-reservoir ratio decreased by 41% (P < 0.03). Similarly, after pericardiotomy, early conduit function fell to 0.14 (SD 0.09) (P < 0.004), reservoir function increased to 0.72 (SD 0.08) (P < 0.04), and, consequently, the early conduit-to-reservoir ratio decreased by 63% (P < 0.006). Cardiac output was inversely related to the conduit-to-reservoir ratio (r = 0.39, P < 0.001). This study demonstrated that the right atrium adjusts its ability to act more as a reservoir than a conduit in a dynamic manner. The RA conduit-to-reservoir ratio was directly related to the right ventricular pressure-RA pressure gradient at the time of maximum RA volume, with increased ventricular pressures favoring conduit function, but it was inversely related to cardiac output, with an increase in the reservoir contribution favoring improved cardiac output.     

Ouabain-induced hypertension enhances left ventricular contractility in rats

Chronic ouabain treatment produces hypertension acting on the central nervous system and at vascular levels. However, cardiac effects in this model of hypertension are still poorly understood. Hence, the effects of hypertension induced by chronic ouabain administration ( approximately 8 microg day(-1), s.c.) for 5 weeks on the cardiac function were studied in Wistar rats. Ouabain induces hypertension but not myocardial hypertrophy. Awake ouabain-treated rats present an increment of the left ventricular systolic pressure and of the maximum positive and negative dP/dt. Isolated papillary muscles from ouabain-treated rats present an increment in isometric force, and this effect was present even when inotropic interventions (external Ca(2+) increment and increased heart rate) were performed. However, the sarcoplasmic reticulum activity and the SERCA-2 protein expression did not change. On the other hand, the activity of myosin ATPase increased without changes in myosin heavy chain protein expression. In addition, the expression of alpha(1) and alpha(2) isoforms of Na(+), K(+)-ATPase also increased in the left ventricle from ouabain-hypertensive rats. The present results showed positive inotropic and lusitropic effects in hearts from awake ouabain-treated rats, which are associated with an increment of the isometric force development and of the activity of myosin ATPase and expression of catalytic subunits of the Na(+), K(+)-ATPase.     

Colchicine attenuates left ventricular hypertrophy but preserves cardiac function of aortic-constricted rats.

To investigate the effects of colchicine on left ventricular (LV) function and hypertrophy (LVH) of rats subjected to constriction of transverse aorta (TAoC), we evaluated SO (sham operated, vehicle; n = 25), SO-T (sham operated, colchicine 0.4 mg/kg body wt ip daily; n = 38), TAoC (vehicle; n = 37), and TAoC-T (TAoC, colchicine; n = 34) on the 2nd, 6th, and 15th day after surgery. Colchicine attenuated LVH of TAoC-T compared with TAoC rats, as evaluated by ratio between LV mass (LV(M)) and right ventricular mass, LV wall thickness, and average diameter of cardiac myocytes. Systolic gradient across TAoC ( approximately 45 mmHg), LV systolic pressure, LV end-diastolic pressure, and rate of LV pressure increase (+dP/dt) were comparable in TAoC-T and TAoC rats. However, the baseline and increases of LV systolic pressure-to-LV(M) and +dP/dt-to-LV(M) ratios induced by phenylephrine infusion were greater in TAoC-T and SO-T compared with SO rats. Baseline and increases of +dP/dt-to-LV(M) ratio were reduced in TAoC compared with SO rats. TAoC rats increased polymerized fraction of tubulin compared with SO, SO-T, and TAoC-T rats. Our results indicate that colchicine treatment reduced LVH to pressure overload but preserved LV function.     

Effects of milrinone on left ventricular cardiac function during cooling in an intact animal model

A significant reduction in immunogenicity has been observed in some frozen-thawed tissues after cryopreservation. The objective of this study was to evaluate the effects of programmed cryopreservation on immunogenicity of rabbit bladder mucosa and on the extent of immunological rejection caused by the allograft. This study would provide theoretical support for the application of allogenic frozen-thawed bladder mucosa in the treatment of urethral stricture. Forty-two adult male New Zealand rabbits were used in this study. The immunogenicity was detected by mixed lymphocyte reaction using the allograft of bladder mucosa (fresh and frozen-thawed) and spleen lymphocytes. Twelve urethral stricture models were established in New Zealand rabbits for substitution urethroplasty using the allograft of bladder mucosa, which were divided into fresh and frozen-thawed group. Two weeks after operation, lymphocyte proliferation was detected in both blood and spleen of recipient rabbits. At the same time, immunohistochemical staining of urethral allograft was performed and the expression of CD3, CD4 and CD8 were observed. The mRNA of bladder mucosa (fresh and frozen-thawed) was extracted and the expressions of RLA-I, RLA-II and RLA-III gene were detected by real-time PCR. By mixed lymphocyte reaction, we found that allogenic lymphocyte proliferation stimulated by frozen-thawed bladder epithelial cells was significantly weaker than that of the fresh cells. The blood and spleen lymphocytes from fresh bladder mucosa group showed significantly higher proliferation rate than frozen-thawed group. Compared with the fresh group, the expression of CD3+ and CD8+ T cells infiltrated in the operation locus of bladder mucosa urethroplasty was significantly decreased in the frozen-thawed group. However, the expressions of RLA genes did not change significantly after the freeze-thaw procedure. This study demonstrates for the first time that a programmed freeze-thaw procedure of rabbit bladder mucosa could reduce its immunogenicity in allogenic bladder mucosa urethroplasty and thus restrict the extent of immunological rejection, therefore, provides theoretical support for the application of frozen-thawed bladder mucosa in the treatment of urethral stricture.     

Stiffness- and relaxation-based quantitation of radial left ventricular oscillations: elucidation of regional diastolic function mechanisms.

Traditionally, global and longitudinal (i.e., regional) left ventricular (LV) diastolic function (DF) assessment has utilized features of transmitral Doppler E and A waves or Doppler tissue imaging (DTI)-derived mitral annular E' and A' waves, respectively. Quantitation of regional DF has included M-mode echocardiography-based approaches and strain and strain rate imaging (in selected imaging planes), while analysis of mitral annular "oscillations" has recently provided a new window into longitudinal (long-axis) function. The remaining major spatial degree of kinematic freedom during diastole, radial (short-axis) motion, has not been fully characterized, nor has it been exploited for its potential to provide radial LV stiffness (k'(rad)) and relaxation/damping (c'(rad)) indexes. Prior characterization of regional (longitudinal) DF used only annular E'- and A'-wave peak velocities or, alternatively, myocardial strain and strain rate. By kinematically modeling short-axis tissue motion as damped radial oscillation, we present a novel method of estimating k'(rad) and c'(rad) during early filling. As required by the (near) constant-volume property of the heart and tissue/blood incompressibility, in subjects (n = 10) with normal DF, we show that oscillation duration-determined longitudinal (k'(long) and c'(long)) and radial (k'(long) and c'(rad)) parameters are highly correlated (R = 0.69 and 0.92, respectively). Selected examples of diabetic and LV hypertrophic subjects yield radial (k'(long) and c'(rad)) parameters that differ substantially from controls. Results underscore the utility of the incompressibility-based causal relation between DTI-determined mitral annular long-axis (longitudinal mode) and short-axis (radial mode) oscillations in healthy subjects. Selected pathological examples provide mechanistic insight and illustrate the value and potential role of regional (longitudinal and radial) DF indexes in fully characterizing normal vs. impaired DF states.     

Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction

In the present study, we investigated whether mesenchymal stem cells (MSCs) overexpressing integrin-linked kinase (ILK) might regulate ventricular remodeling and cardiac function in a porcine myocardial infarction model. ILK-modified MSCs (ILK-MSCs) (n = 8), MSCs (n = 8) or placebo (n = 8) were injected into peri-infarct myocardium 7 days after ligation of the left anterior descending coronary artery. ILK expression was confirmed by immunofluorescence, real-time PCR, Western blot analysis, and flow cytometry. In vitro assays indicated increased proliferation and reduced apoptosis of MSCs due to overexpression of ILK. Echocardiographic, single-photon emission computed tomography and positron emission tomography analyses demonstrated preserved cardiac function and myocardial perfusion. Reduced fibrosis, increased cardiomyocyte proliferation, and enhanced angiogenesis were observed in the ILK-MSC group. Reduced apoptosis, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis, was also noted. In conclusion, ILK promotes MSC proliferation and suppresses apoptosis. ILK-MSC transplantation improves ventricular remodeling and cardiac function in pigs after MI. It is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of post-infarct remodeling and subsequent heart failure.     

Comprehensive assessment of left ventricular myocardial function by two-dimensional speckle-tracking echocardiography

Background

Left ventricular ejection fraction (LVEF) results from the combined action of longitudinal and circumferential contraction, radial thickening, and basal and apical rotation. The study of these parameters together may lead to an accurate assessment of the cardiac function.

Methods

Ninety healthy volunteers, categorized by gender and age (≤ 55 and?>? 55 years), were evaluated using two-dimensional speckle tracking echocardiography. Transversal views of the left ventricle (LV) were obtained to calculate circumferential strain and left ventricular twist, while three apical views were obtained to determine longitudinal strain (LS) and mitral annular plane systolic excursion (MAPSE). We established the integral myocardial function of the LV according to: 1. The Combined Deformation Parameter (CDP), which includes Deformation Product (DP) - Twist x LS (° x %) - and Deformation Index (DefI) -Twist / LS (° / %)-; and 2. the Torsion Index (TorI): Twist / MAPSE (° / cm).

Results

The mean age of our patients was 50.3?±?11.1 years. CDP did not vary with gender or age. The average DP was ??432?±?172 ° x %, and the average DefI was ??0.96?±?0.36 ° / %. DP provides information about myocardial function (normal, pseudonormal, depressed), and the DefI quotient indicates which component (s) is/are affected in cases of abnormality. TorI was higher in volunteers over 55 years (16.5?±?15.2 vs 13.1?±?5.0 °/cm, p?=?0.003), but did not vary with gender.

Conclusions

The proposed parameters integrate values of twisting and longitudinal shortening. They allow a complete physiological assessment of cardiac systolic function, and could be used for the early detection and characterization of its alteration.

     

Zerumbone prevents pressure overload-induced left ventricular systolic dysfunction by inhibiting cardiac hypertrophy and fibrosis

BackgroundCardiac hypertrophy and fibrosis are hallmarks of cardiac remodeling and are involved functionally in the development of heart failure (HF). However, it is unknown whether Zerumbone (Zer) prevents left ventricular (LV) systolic dysfunction by inhibiting cardiac hypertrophy and fibrosis.PurposeThis study investigated the effect of Zer on cardiac hypertrophy and fibrosis in vitro and in vivo.Study Design/methodsIn primary cultured cardiac cells from neonatal rats, the effect of Zer on phenylephrine (PE)-induced hypertrophic responses and transforming growth factor beta (TGF-β)-induced fibrotic responses was observed. To determine whether Zer prevents the development of pressure overload-induced HF in vivo, a transverse aortic constriction (TAC) mouse model was utilized. Cardiac function was evaluated by echocardiography. The changes of cardiomyocyte surface area were observed using immunofluorescence staining and histological analysis (HE and WGA staining). Collagen synthesis and fibrosis formation were measured by scintillation counter and picrosirius staining, respectively. The total mRNA levels of genes associated with hypertrophy (ANF and BNP) and fibrosis (Postn and α-SMA) were measured by qRT-PCR. The protein expressions (Akt and α-SMA) were assessed by western blotting.ResultsZer significantly suppressed PE-induced increase in cell size, mRNA levels of ANF and BNP, and Akt phosphorylation in cardiomyocytes. The TGF-β-induced increase in proline incorporation, mRNA levels of Postn and α-SMA, and protein expression of α-SMA were decreased by Zer in cultured cardiac fibroblasts. In the TAC male C57BL/6 mice, echocardiography results demonstrated that Zer improved cardiac function by increasing LV fractional shortening and reducing LV wall thickness compared with the vehicle group. ZER significantly reduced the level of phosphorylated Akt both in cultured cardiomyocytes treated with PE and in the hearts of TAC. Finally, Zer inhibited the pressure overload-induced cardiac hypertrophy and cardiac fibrosis.ConclusionZer ameliorates pressure overload-induced LV dysfunction, at least in part by suppressing both cardiac hypertrophy and fibrosis.     

Anthrax toxins induce shock in rats by depressed cardiac ventricular function

Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx) and edema toxin (EdTx) to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA) toxin component at various time points after infusion. Peak serum levels of PA were in the microg/mL range with half-lives of 10-20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the microg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections.     

Effect of milrinone on left ventricular relaxation and Ca(2+) uptake function of cardiac sarcoplasmic reticulum

Milrinone, a phosphodiesterase 3 (PDE3) inhibitor, is known to enhance left ventricular (LV) contractility by an inhibition of the breakdown of cAMP through the mechanism inhibiting PDE3. However, it is unclear whether milrinone also exerts positive lusitropy, like dobutamine. Here, we assessed the effects of milrinone on in vivo LV relaxation, as well as the Ca(2+)-ATPase activity and the Ca(2+) uptake function of the cardiac sarcoplasmic reticulum (SR), compared with the effect of dobutamine on those functions. After dobutamine (3 microg x kg(-1) x min(-1)) was administered, the peak value of the first derivative of LV pressure (+dP/dt) increased by 46%, whereas the time constant (tau) of LV pressure decay decreased by 6.9%, respectively. After milrinone (10 microg/kg) was administered, the peak +dP/dt increased to a similar extent as dobutamine (46%), whereas tau decreased much more than dobutamine (19.9%; P < 0.05). In LV crude homogenate, the thapsigargin-sensitive, Ca(2+)-ATPase activity-cAMP relationships was significantly less increased by milrinone compared with dobutamine (P < 0.05), indicating the higher sensitivity of the SR Ca(2+)-ATPase activity on cAMP by milrinone than by dobutamine. In the SR vesicles purified from LV muscles, the addition of cAMP increased the SR Ca(2+) uptake in a dose-dependent fashion, and the PDE3 inhibitors (milrinone and cGMP) significantly augmented this response (P < 0.05). Hence, milrinone substantially improved LV relaxation in association with an acceleration of the SR Ca(2+)-ATPase activity and the SR Ca(2+) uptake. This acceleration might be due to an inhibition of the membrane-bound PDE3 in the SR, leading to a local elevation of cAMP.     

Interrelationships between left ventricular volume and output during exercise in healthy subjects.

To better characterize the relationship between left ventricular volume response and improved ventricular ejection and output during supine exercise in normal subjects, 36 healthy asymptomatic volunteers (age 39 +/- 17 yr) were studied with radionuclide ventriculography during recumbent bicycle ergometry. Relative changes in left ventricular end-diastolic and end-systolic volume were measured at rest and during exercise by a modification of the radionuclide counts-based method that accounted for variability in stress blood pool counts. A biphasic response was noted in left ventricular end-diastolic volume with an initial increase in early exercise (8.5 +/- 11% at 200 kpm/min and 11 +/- 12% at 300 kpm/min) followed by a progressive and significant decline at peak exercise (-3.3 +/- 18% at 547 +/- 140 kpm/min; P < 0.05). There was substantial variation in end-diastolic volume response at peak exercise in the group as a whole, which could be more closely related to changes in end-systolic volume (r = 0.84, P < 0.0001) than in heart rate (r = -0.57, P < 0.01) or age (r = 0.36, P < 0.05) of the study subjects. Despite the decline in ventricular filling, systolic function appeared to improve dramatically at peak exercise (change in left ventricular ejection fraction 15.5 +/- 6.4, P < 0.0001). Although not directly related to increasing systolic ejection, end-diastolic volume was directly related to the percent change in stroke volume at peak exercise among the study subjects (r = 0.88, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性低氧对大鼠左右心室的功能及TRPC亚家族表达的影响

目的：探讨慢性低氧3周对大鼠左右心室的影响以及规范性瞬时感受器电位亚家族（TRPC）在慢性低氧诱导的右心室心肌肥厚中的表达。方法：将SD雄性大鼠48只随机分为对照组（CON组）和慢性低氧肺动脉高压模型组（CH组）（n=24）,CH组将大鼠置于连续的慢性低氧（10％±0．2％）环境饲养三周以诱导大鼠发生心肌肥厚。通过左、右心室插管法测定右心室内压（RVSP）、左心室内压（LVSP）、心率（HR）、平均体循环动脉压（mSAP）、左、右心室内压力最大上升速率（＋dp／dtmax）、最大下降速率（-dp／dkmax）、右心肥大指数（RVMI）、左心肥大指数（LVMI）;HE染色观察左、右心室心肌组织切片;通过SYBR Green荧光定量PCR法检测CON组、CH组大鼠的肥厚侧心室心肌组织编码TRPC 1／3／4／5／6／7的rnRNA表达;结合real-time RT-PCR结果对mRNA表达有显著变化的TRPC亚型通过免疫印迹法检测相应蛋白的表达。结果：与CON组相比：CH组的RVSP、RVMI、右心室±dp／dtmax显著增高（P〈0．01）,LVSP、左心室±dp／dmax无显著变化,LVMI显著降低（P〈0．01）;CH组右心室心肌细胞显著增粗（P〈0．01）,细胞内肌原纤维数量增多,心肌纤维排列紊乱,细胞核深染,形状不整;左心室心肌纤维无明显改变;CH组编码TRPCI的mRNA和蛋白显著增高（P〈0．05）,而编码其余TRPC亚型的mRNA无显著变化。结论：慢性低氧3周可特异性诱导sD大鼠产生右心室心肌肥厚,上调了编码右心室心肌细胞TRPCI通道蛋白的mRNA和蛋白的表达,TRPCI可能参与了心肌肥厚的发生发展。