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PubMed2005

Calcium receptor is functionally expressed in rat neonatal ventricular cardiomyocytes.

Both intra- and extracellular calcium play multiple roles in the physiology and pathophysiology of cardiomyocytes, especially in stimulus-contraction coupling. The intracellular calcium level is closely controlled through the concerted actions of calcium channels, exchangers, and pumps; however, the expression and function(s) of the so-called calcium-sensing receptor (CaR) in the heart remain less well characterized. The CaR is a seven-transmembrane receptor, which, in response to noncovalent binding of extracellular calcium, activates intracellular effectors, including G proteins and extracellular signal-regulated kinases (ERK1/2). We have shown that cultured neonatal cardiomyocytes express the CaR messenger RNA and the CaR protein. Furthermore, increasing concentrations of extracellular calcium and a type II CaR activator "calcimimetic" caused inositol phosphate (IP) accumulation, downregulated tritiated thymidine incorporation, and supported ERK1/2 phosphorylation, suggesting that the CaR protein is functionally active. Interestingly, the calcimimetic induced a more rapid ERK1/2 phosphorylation than calcium and left-shifted the IP concentration-response curve for extracellular calcium, supporting the hypothesis that CaR is functionally expressed in cardiac myocytes. This notion was underscored by studies using a virus containing a dominant-negative CaR construct, because this protein blunted the calcium-induced IP response. In conclusion, we have shown that the CaR is functionally expressed in neonatal ventricular cardiomyocytes and that the receptor activates second messenger pathways, including IP and ERK, and decreases DNA synthesis. A specific calcium-sensing receptor on cardiac myocytes could play a role in regulating cardiac development, function, and homeostasis.

Animals↗
PubMed1995

Down-regulation of the IGF-1 system parallels the attenuation in the proliferative capacity of rat ventricular myocytes during postnatal development.

BACKGROUND: Insulin-like growth factor-1 receptor (IGF-1R) and its ligand (IGF-1) have been implicated in the growth of several cell types, including ventricular myocytes. However, the growth-promoting effect of this pathway on myocyte hypertrophy and hyperplasia has not been determined. During early postnatal development, myocyte cell volume increases nearly 25-fold, and myocyte proliferation is markedly attenuated, so a progressive decrease in this signaling mechanism will indicate that the IGF-1-IGF-1R system is mostly involved in cell proliferation. Conversely, a continuous increase in the expression of IGF-1 and IGF-1R in myocytes with maturation will suggest its involvement in cellular hypertrophy. DESIGN: Myocytes were isolated from fetal rats and from rats at 1, 5, 11, 21, 35, and 60 days of age. Total RNA was extracted from these cells, and the expression of IGF-1, IGF-2, IGF-1R, and DNA polymerase alpha was measured by reverse transcriptase-PCR. IGF-1R mRNA levels were also determined by RNase protection assay, and the changes in IGF-1R protein were determined by the cross-linking technique. Finally, the expression of late growth-related genes was determined and compared with the fraction of muscle cells synthesizing DNA. These analyses were restricted to the left ventricular free wall and septum combined. RESULTS: Myocardial development was characterized by a progressive decrease in the expression of late growth-related genes in myocytes, which was particularly evident at 21 days after birth and persisted up to 2 months of age. The expression of IGF-2 in these cells decreased at birth, whereas the attenuation in IGF-1 mRNA became apparent a few days later during postnatal development. The induction of IGF-1R at the message and protein levels decreased by 11 days, and this phenomenon was more evident at the subsequent age intervals. Moreover, DNA synthesis in myocytes was sharply reduced at 21 days after birth. CONCLUSIONS: In conclusion, the decline in myocyte proliferation with cardiac development appears to be coupled with attenuation of the IGF-1-IGF-1R system, which may condition the changes in late growth-regulated genes, DNA replication, and cellular mitotic division in the myocardium.

Aging↗
PubMed2004

The two-minute walk test as a measure of functional capacity in cardiac surgery patients.

OBJECTIVE: To examine construct validity and sensitivity of the two-minute walk test (2MWT) in cardiac surgery patients. DESIGN: Measurements were made in patients preoperatively, during the postoperative in-hospital stay, and 6 to 8 weeks after discharge from hospital. SETTING: Ambulatory and hospitalized care. PARTICIPANTS: Patients (N=122; mean age +/- standard deviation, 63+/-9 y) undergoing coronary artery bypass grafting. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The 2MWT, New York Heart Association (NYHA) functional classification for cardiac disease, the Nottingham Extended Activities of Daily Living scale, and the Medical Outcomes Survey 36-Item Short-Form Health Questionnaire (SF-36). RESULTS: Distance walked in 2 minutes decreased significantly postoperatively (from 138+/-26 m to 84+/-33 m, P<.001), but increased again at follow-up (151+/-31 m, P<.0001). Distance walked on the 2MWT correlated significantly to SF-36 (physical function subscale) preoperatively (r=.44) and at follow-up (r=.48) (P<.001). There was a significant difference in distance walked between those with NYHA class I and II compared with those classified as III or IV (P=.04). However, there was no significant difference in distance walked in 2 minutes between those who developed cardiac or pulmonary complications postoperatively (P> or =0.2). CONCLUSIONS: The 2MWT was sensitive to change after cardiac surgery and showed moderate correlation with measures of physical functioning in this population. However, the 2MWT could not identify those who developed complications in the postoperative period.

Activities of Daily Living↗
PubMed2003

Characterization and regulation of T-type Ca2+ channels in embryonic stem cell-derived cardiomyocytes.

T-type Ca2+ channels may play a role in cardiac development. We studied the developmental regulation of the T-type currents (ICa,T) in cardiomyocytes (CMs) derived from mouse embryonic stem cells (ESCs). ICa,T was studied in isolated CMs by whole cell patch clamp. Subsequently, CMs were identified by the myosin light chain 2v-driven green fluorescent protein expression, and laser capture microdissection was used to isolate total RNA from groups of cells at various developmental time points. ICa,T showed characteristics of Cav3.1, such as resistance to Ni2+ block, and a transient increase during development, correlating with measures of spontaneous electrical activity. Real-time RT-PCR showed that Cav3.1 mRNA abundance correlated (r2 = 0.81) with ICa,T. The mRNA copy number was low at 7+4 days (2 copies/cell), increased significantly by 7+10 days (27/cell; P < 0.01), peaked at 7+16 days (174/cell), and declined significantly at 7+27 days (25/cell). These data suggest that ICa,T is developmentally regulated at the level of mRNA abundance and that this regulation parallels measures of pacemaker activity, suggesting that ICa,T might play a role in the spontaneous contractions during CM development.

Animals↗
PubMed2005

Metabolic syndrome and cardiac disease in Japanese men: applicability of the concept of metabolic syndrome defined by the National Cholesterol Education Program-Adult Treatment Panel III to Japanese men--the Tanno and Sobetsu Study.

Results of a 6-year follow-up study were used to determine whether the concept of and the criteria for metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) can be applied to Japanese men for prediction of the occurrence of cardiac disease. The subjects were 808 men who underwent mass health check-ups in 1993 and who were not on medication for hypertension, diabetes or hyperlipidemia. Individuals who had hypertriglyceridemia, hypo-high density lipoprotein (HDL) cholesterolemia, high blood pressure, and/or high fasting plasma glucose levels were identified on the basis of the NCEP-ATP III criteria. Not in conformity with the NCEP-ATP Ill, however, a cut-off value of 85 cm was used for waist girth as an indicator of abdominal obesity. The subjects who had 3 or more risk factors were judged as having metabolic syndrome. The proportion of subjects having metabolic syndrome was 25.3%. In the 6-year follow-up study, cardiac disease occurred in 11.7% of the subjects in the metabolic syndrome group and in 6.7% of the subjects in the non-metabolic syndrome group. Results of regression analysis using Cox's proportional hazards model showed that subjects in the metabolic syndrome group had a 2.2-times greater risk of developing cardiac disease than did subjects in the non-metabolic syndrome group. The concept of metabolic syndrome as defined in the NCEP-ATP III was therefore considered to be useful for predicting the occurrence of cardiac disease in Japanese men.

Aged↗
PubMed2001

Comparison of connexin 43, 40 and 45 expression patterns in the developing human and mouse hearts.

The mouse is currently widely used as a model organism in the analysis of gene function but how developmentally regulated patterns of connexin gene expression in the mouse compare with those in the human is unclear. Here we compare the patterns of connexin expression in the heart during the development of the mouse (from embryonic day 12.5 to 6 weeks postpartum) and the human (at 9 weeks gestation and adult stage). The extent of connexin43 expression in the ventricles progressively increased during development of the mouse heart. The developmental pattern of expression for connexins 40 and 45 in the mouse heart was similar, but not identical, and in the ventricles showed a progressive and preferential expression in the conduction system. In general, these dynamic changes of connexins 43, 40 and 45 during mouse cardiac development appear to be mirrored in the human.

Adult↗
PubMed2003

Identification of plateled-derived growth factor-BB as cardiogenesis-inducing factor in mouse embryonic stem cells under serum-free conditions.

BACKGROUND/AIMS: Embryonic stem (ES) cells may represent an alternative source of functionally mature cardiomyocytes for the treatment of heart diseases. ES cells spontaneously differentiate into spheroidal aggregates, also referred to as embryoid bodies (EBs). The identification of growth factors playing a decisive role in cardiogenesis is a crucial issue for the generation of mature cardiomyocytes. METHODS: In order to identify growth factors promoting cardiac development, we established a new differentiation protocol using a defined serum-replacement medium (SRM) containing 5 microg/ml insulin and 5 microg/ml transferrin in combination with Dulbecco's Modified Eagle Medium (DMEM). Furthermore, we added platelet-derived growth factor-BB (PDGF-BB) or sphingosine-1-phosphate (SPP) to promote cardiac differentiation. RESULTS: Using SRM/DMEM, we obtained a 6-fold increase of cardiac specific myosin heavy chain alpha and beta (cMHCalpha/beta) in relation to 0,2% foetal calf serum (FCS)/DMEM (= 100%). Stimulation of EBs with PDGF-BB in the presence of SRM/DMEM resulted in a further 2,6-fold enhancement in comparison with the SRM/DMEM-induced increase of cMHCalpha/beta (= 100%). A parallel increase in the number of beating EBs was observed. Similar results were obtained after stimulation of EBs with 5 microg/ml SPP. CONCLUSION: We established a serum-free protocol and identify PDGF-BB and SPP as potent factors promoting cardiogenesis in ES cells.

Animals↗
PubMed2006

Intermediate filament protein nestin is expressed in developing kidney and heart and might be regulated by the Wilms' tumor suppressor Wt1.

Nestin is an intermediate filament protein originally described in neural stem cells and a variety of progenitor cells. More recently, nestin was detected in rat kidney podocytes. We show here that nestin is expressed in a developmentally regulated pattern in the kidney. Nestin was detected by immunohistochemistry in the condensing mesenchyme surrounding the ureter, in developing glomeruli, in podocytes of the adult kidney, and in a podocyte cell line. Nestin shared a striking overlap in expression with the Wilms' tumor suppressor Wt1. Nestin was significantly upregulated in a cell line with inducible Wt1 expression upon induction of Wt1. Cotransfection experiments in human embryonic kidney cells (HEK293) revealed stimulation of a nestin intron 2 enhancer element up to six-fold by the Wt1(-KTS) splice variant. Nestin expression was significantly reduced in an inducible mouse model of glomerular disease. This model is based on podocyte-specific overexpression of Pax2 and associated with a loss of Wt1 expression. Furthermore, also in the developing heart, nestin was found in an overlapping pattern with Wt1 in the epicardium and the forming coronary vessels. Strikingly, in the hearts of Wt1 knockout mice, nestin was barely detectable compared with the hearts of wild-type embryos. Our results show that nestin is expressed at different stages of kidney and cardiac development and suggest that its expression in these organs might be regulated by the Wilms' tumor suppressor Wt1.

Animals↗
PubMed2005

Neuregulin receptor ErbB2 localization at T-tubule in cardiac and skeletal muscle.

Previous studies have indicated that ErbB receptors for neuregulins play an important role in cardiac development and muscle spindle formation during embryogenesis; however, little is known about their functions in adulthood. Recent reports indicate that breast cancer therapy with humanized monoclonal ErbB2 antibody induces cardiomyopathy, suggesting that ErbB2 serves as a crucial signaling receptor, even in the adult heart. Here, we examine ErbB2 expression and localization in both cardiac and skeletal muscle of adult mice via immunoblot and immunohistochemistry. ErbB2 was detected as a band approximately 185 kD molecular mass in each cardiac and skeletal muscle extraction. Confocal images of double labeling showed that ErbB2 was colocalized with caveolin-3 in cardiac muscle and with dihydropyridine receptor in skeletal muscle, suggesting that ErbB2 was localized at the T-tubule. In addition, immunoelectron micrographs clearly demonstrated that ErbB2 was located at the T-tubule in both types of muscle. Taken together, the results of the present study suggest that neuregulin-ErbB2 signaling plays a role in the physiological function of cardiac and skeletal muscle, even in adulthood.

Animals↗
PubMed1995

[Cardiopulmonary resuscitation with continuous veno-venous hemofiltration for intraoperative cardiac arrest owing to hypothermia--a case report].

A 77-year-old female was scheduled for an exploratory laparotomy under nitrous oxide-oxygen-neurolept anesthesia. At the time of admission to the operating room, the rectal temperature was 36.0 degrees C. From the beginning of operation, the body temperature dropped slowly despite constant efforts of warming with a blanket and warm intravenous fluids. At 5 hours and 15 minutes after the beginning of operation, she developed cardiac arrest due to hypothermia. At this time the rectal temperature was 31.8 degrees C. In spite of cardioversion and intravenous administration of epinephrine, we could not resuscitate her successfully. Immediately, rewarming was started with continuous veno-venos hemofiltration (CVVH). When the rectal temperature rose to 32.9 degrees C one hour after the rewarming, cardioversion was performed again and spontaneous heart beat was observed. As soon as the rectal temperature rose to 34.0 degrees C, CHF was stopped. Her consciousness recovered 2 hours and 10 minutes after cardiopulmonary resuscitation, we conclude that rewarming with CVVH can be an effective method of cardiopulmonary resuscitation in a patient suffering cardiac arrest due to hypothermia.

Aged↗
PubMed2003

Prognostic value of abnormal vasoreactivity of epicardial coronary arteries to sympathetic stimulation in patients with normal coronary angiograms.

OBJECTIVE: We aimed to evaluate prospectively whether patients with normal coronary angiogram but abnormal epicardial vasoreactivity to cold pressor test (CPT) are at increased risk for cardiovascular events. METHODS AND RESULTS: Vasoreactivity in response to CPT and dilation of epicardial arteries to intracoronary application of nitroglycerin were assessed quantitatively (percent change of luminal area, DeltaLA%) in 130 patients with normal coronary angiograms. Cardiovascular events (cardiovascular death, acute coronary syndrome, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary bypass grafting, ischemic stroke, or peripheral revascularization) were assessed as clinical outcome parameters over a mean follow-up period of 45+/-9 months. Based on their vascular responses to CPT, patients were assigned into the following 3 groups: group 1, patients with normal vasodilator response (DeltaLA >0%; n=37); group 2, patients with moderate vasoconstrictor response (DeltaLA between 0% and -15%; n=42); and group 3, patients with severe vasoconstrictor response (DeltaLA < or =-15%; n=51). Although patients from groups 2 and 3 had significantly increased vasoconstrictor response to CPT (group 2, DeltaLA -6+/-3% and group 3, DeltaLA -24+/-6% versus group 1, DeltaLA 11+/-9%; P< or =0.0001), they showed normal endothelial-independent epicardial vasodilation to intracoronary application of nitroglycerin similar to patients from group 1 (DeltaLA 39+/-16% and 34+/-14% versus 41+/-14%; P=NS, respectively). During follow-up, none of the patients from group 1 developed cardiac events. However, 7 cardiovascular events occurred in group 2 and 30 occurred in group 3 in 4 and 22 patients, respectively (P< or =0.0001, univariate by log-rank test). After adjustment for known risk factors for coronary artery disease, impaired epicardial coronary vasoreactivity to CPT remained significantly associated with the risk of developing cardiovascular events (P=0.040, multivariate by Cox regression model). CONCLUSIONS: In patients with normal coronary angiogram, abnormal vasoreactivity of epicardial coronary arteries in response to sympathetic stimulation is associated with the risk of developing cardiovascular events.

C-Reactive Protein↗
PubMed2001

PlexinA2 and semaphorin signaling during cardiac neural crest development.

Classic studies using avian model systems have demonstrated that cardiac neural crest cells are required for proper development of the cardiovascular system. Environmental influences that perturb neural crest development cause congenital heart defects in laboratory animals and in man. However, little progress has been made in determining molecular programs specifically regulating cardiac neural crest migration and function. Only recently have complex transgenic tools become available that confirm the presence of cardiac neural crest cells in the mammalian heart. These studies have relied upon the use of transgenic mouse lines and fate-mapping studies using Cre recombinase and neural crest-specific promoters. In this study, we use these techniques to demonstrate that PlexinA2 is expressed by migrating and postmigratory cardiac neural crest cells in the mouse. Plexins function as co-receptors for semaphorin signaling molecules and mediate axon pathfinding in the central nervous system. We demonstrate that PlexinA2-expressing cardiac neural crest cells are patterned abnormally in several mutant mouse lines with congenital heart disease including those lacking the secreted signaling molecule Semaphorin 3C. These data suggest a parallel between the function of semaphorin signaling in the central nervous system and in the patterning of cardiac neural crest in the periphery.

Animals↗
PubMed2006

JNK1 is required to preserve cardiac function in the early response to pressure overload.

Cardiac stress consistently activates c-Jun NH(2)-terminal kinase (JNK) pathways, however the role of different members of the JNK family is unclear. In this study, we applied pressure overload (TAC) in mice with selective deletion of the three JNK genes (Jnk1(-/-), Jnk2(-/-), and Jnk3(-/-)). Following TAC, all three JNK knockout mouse lines developed cardiac hypertrophy similar to wild-type mice (WT), but only JNK1(-/-) mice displayed a significant reduction in fractional shortening after 3 and 7 days of pressure overload, associated with a significant increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and marked inflammatory infiltrate. After the acute deterioration stage, JNK1(-/-) mice underwent a slow recovery followed by a steady progression of cardiac dysfunction, becoming indistinguishable from WT after 12 weeks of TAC. These data suggest that JNK1 plays a protective role in response to pressure overload, preventing the early deterioration in cardiac function following an acute increase in afterload.

Animals↗
PubMed1996

Characterization of human B creatine kinase gene regulation in the heart in vitro and in vivo.

During cardiogenesis, genes indicative of the adult phenotype are transcriptionally activated while genes characteristic of the embryonic phenotype are down-regulated. The regulation of embryonic genes such as the brain isoform of creatine kinase (BCK) during cardiac development has not been characterized. Accordingly, the transcriptional regulation of BCK in the developing heart was determined. In vitro and in vivo promoter analyses of the human BCK gene identified an element between +25 and +57 that functioned as an enhancer. Electromobility shift assays using adult and neonatal nuclear extracts identified a specific complex binding this element, the abundance of which correlated with the developmental level of endogenous cardiac BCK expression. Mutations at +47 and +53 led to a loss of activity in transfected cells and obviated binding in electromobility shift assays. These data show that a nuclear factor in cardiocytes interacts with an enhancer element (+25 and +57), via nucleotides +47 and +53, to drive BCK expression in the heart and suggest that developmental BCK expression is via abundance of this factor. The nuclear factor has not been identified but as described previously binding sites are not present in the enhancer, it is either a known factor interacting with a new recognition site or a new factor.

Aging↗
PubMed2004

Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal lymphoblastic lymphoma.

Lymphoblastic lymphoma, an aggressive mediastinal mass, is recognized as serious threat to the patient in developing cardiac tamponade or airway obstruction. Surgical procedure is often required to relieve clinical emergency and to establish prompt pathological diagnosis. However, in such a patient, acute respiratory occlusion in the spine position can be a life-threatening complication during general anesthesia. We describe a 17-year-old man whose cardiac tamponade was treated by pericardial-pleural window through a left anterior thoracotomy in the lateral position. The patient recovered from hemodynamic compromise without showing respiratory occlusion during general anesthesia and remained in the lateral position until extubation. Pathological diagnosis was precursor T-lymphoblastic lymphoma. There were no complications attributable to the operative procedure. Further chemotherapy reduced the mediastinal mass in size after two weeks when the patient developed sepsis and died. Lateral position prevents respiratory occlusion during surgical procedure under general anesthesia in the patient of huge anterior mediastinal tumor with airway obstruction.

Adolescent↗
PubMedDate not supplied

Radionuclide ejection fraction in doxorubicin cardiotoxicity.

Serial assessment of cardiac function by radionuclide ejection fraction (EF), using a "first-pass" technique, was performed prior to each dose in 292 patients receiving doxorubicin. Detailed analysis was undertaken in 98 patients, consisting of all 91 patients who had received greater than 200 mg/m2 and seven with risk factors (RFs) who had received between 100 and 200 mg/m2. Thirty-two patients had RFs and 66 had no risk factors (NRFs). RFs were: (a) cardiovascular disease, (b) mediastinal irradiation within 6 months of starting doxorubicin treatment, and (c) total doxorubicin dose greater than 550 mg/m2. The criteria for discontinuing doxorubicin were EF less than 0.40 in RF patients or less than 0.35 in NRF patients or decrease in EF of greater than or equal to 0.14 over three successive readings. In the NRF group, no patient met these criteria nor did any develop cardiac failure. In the RF group, discontinuation was indicated in eight patients: two stopped receiving doxorubicin at total doses of 730 mg/m2 and 680 mg/m2, respectively, and it was discontinued in the other six at total doses ranging from 120 to 420 mg/m2. Prior to the first dose of doxorubicin, all patients should have a baseline EF and assessment of RFs. An EF study is required before each subsequent dose in patients with RFs or with initial EF less than 0.45, but in the remaining patients, serial studies are not required until there is a cumulative dose of 450 mg/m2. Use of these guidelines and our criteria for discontinuation may prevent development of doxorubicin cardiotoxicity.

Adolescent↗
PubMed2000

Complete sequence and characterization of chick ventricular myosin heavy chain in the developing atria.

We isolated five complementary DNA (cDNA) clones, encoding the chick ventricular myosin heavy chain (MyHC) by reverse transcription polymerase chain reaction (RT-PCR). The entire cDNA consists of 5995 nucleotides with the 52 bp 5'-untranslated region and the 129 bp 3'-untranslated region. The complete cDNA encodes 1937 amino acids. Expression of the chick ventricular MyHC gene was also studied by Northern blot analysis. This gene continued to be strongly expressed in the ventricle during cardiac development. On the other hand, its expression was moderate in the early embryonic atria, and was down-regulated during development. In the adult atria, this gene was expressed at very low levels. To determine the localization of the ventricular MyHC protein, an immunohistochemical study was performed. The ventricular MyHC was present in early embryonic atrial myocytes. During development, the expression of this protein in the atrial myocytes was down-regulated, but continued to be present in the atrial conduction system. Our results indicate that the ventricular MyHC appears in the primary atrial myocardium and is then localized in the conduction cells of the atria.

Animals↗
PubMed2000

The cardiac beta-adrenoceptor-G-protein(s)-adenylyl cyclase system in monocrotaline-treated rats.

In rats, injection of the alkaloid monocrotaline (MCT) causes right ventricular hypertrophy and cardiac failure. In order to study whether, in MCT-treated rats, changes in the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system might be comparable to those found in human primary pulmonary hypertension, we assessed in right and left ventricles from MCT-treated rats the components of the beta -adrenoceptor system: the receptor number and subtype distribution (by (-)-[(125)I]iodocyanopindolol binding), the G-proteins (by quantitative Western blotting), and the activity of adenylyl cyclase. A single injection of 60 mg/kg i.p. MCT caused in rats right ventricular hypertrophy (RVH); part of the rats developed cardiac failure (RVF). In these rats the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system was markedly changed beta -adrenoceptors were desensitized due to a decrease in receptor number, an uncoupling of the receptor from the G(s)-adenylyl cyclase system, a decrease in G(s)and a decrease in the activity of the catalytic unit of adenylyl cyclase. In general, these changes were more pronounced in right ventricles v left ventricles, and in rats with RVF v rats with RVH. On the other hand, cardiac muscarinic receptors and G(i)appeared not to be altered. We conclude that in MCT-treated rats changes in the cardiac beta -adrenoceptor-G-protein(s)-adenylyl cyclase system occur that resemble those observed in human primary pulmonary hypertension. Thus, MCT-treated rat appears to be a suitable animal model to study in more detail the pathophysiology of the development of right heart failure, and to identify new therapeutic possibilities.

Adenylyl Cyclases↗