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Development and structures of the venous pole of the heart.

In the past, our interpretations of cardiac development depended on analysis of serially sectioned embryos, supported by three-dimensional reconstructions. It was not possible, using these techniques, to trace the fate of the various embryonic building blocks. This has all changed with the advent of the new techniques in molecular biology. Combining our experience with these new techniques and our previous studies using the classic approach, we have reviewed how the recent advances clarify controversies that still exist concerning the development of the venous pole. The arguments devolve on whether the pulmonary vein is itself a new development or whether its primordium is derived from the systemic venous tributaries, the so-called sinus venosus. The new techniques show that, rather than developing in the form of a segmented tube, the heart is built up by addition of material to both its arterial and venous poles. At no stage is it possible to recognize a discrete part of the tube that can be identified as the sinus venosus. The confluence of the systemic venous tributaries does not become recognizable as a discrete anatomic entity until compartmented into the newly formed right atrium concomitant with formation of the venous valves. The new molecular techniques show that the pulmonary vein is a new structure, anatomically and developmentally, that is derived from mediastinal myocardium. It gains its connection to the morphologically left atrium between the right- and left-sided systemic venous tributaries.

Animals↗

Detection of iatrogenic cardiac tamponade by transesophageal echocardiography during vena cava filter procedure.

PURPOSE: To present a patient who developed cardiac tamponade during insertion of an inferior vena cava (IVC) filter. Intraoperative transesophageal echocardiography (TEE) was used as a means to diagnose the cardiac tamponade and to facilitate guiding of pericardiocentesis. CLINICAL FEATURES: A 45-yr-old man with protein S deficiency complicated by repeated attacks of deep vein thrombosis and pulmonary thromboembolism was scheduled for insertion of an IVC filter. He had history of chronic renal insufficiency, heart failure, and cerebral infarction with mild left hemiparesis. Current medication included diltiazem (30 mg, I tab tid ), prednisolone (5 mg, 2 tabs qd ), and warfarin (2.5 mg daily). Preoperative transthoracic echocardiography demonstrated bilateral pleural effusions, moderate mitral regurgitation and tricuspid regurgitation, left atrial appendage thrombus and severe generalized hypokinesia of left ventricle. Nuclear medicine examination by (99)Tc showed ejection fractions of left ventricle and right ventricle as 20% and 22%, respectively. Under the impression of protein S deficiency with multiple attacks of thromboembolism and failure of anticoagulant therapy, he was arranged for the procedure of vena caval filter insertion. Unfortunately, iatrogenic cardiac tamponade occurred during the course of the procedure with rapid hemodynamic deterioration. Because of the expedient of routine monitoring of cardiac condition with TEE, a prompt diagnosis was made. We successfully improved the patient's hemodynamic status after transthoracic echo-guided pericardiocentesis. CONCLUSION: Intraoperative TEE is recommended to be used routinely in patients undergoing vena cava filter procedures. The availability of echocardiographic monitoring in the operation room allows the confirmation of the diagnosis and facilitation pericardiocentesis.

Cardiac Tamponade↗

Cardiac arrhythmogenic action of benzo(a)pyrene in the rabbit.

Rabbits treated with benzo(a)pyrene developed cardiac arrhythmias when exposed by inhalation to 8100 ppm trichloroethylene or 15000 ppm halothane to a greater extent and at lower doses of epinephrine challenge than did controls. Benzo(a)pyrene and 3-methylcholanthrene both increased the metabolism of trichloroethylene, but 3-methylcholanthrene did not increase its cardiotoxic effect. The basis of the arrythmogenic action of benzo(a)pyrene appears to be unrelated to its ability to induce xenobiotic metabolism.

Animals↗

A new tinman-related gene, nkx2.7, anticipates the expression of nkx2.5 and nkx2.3 in zebrafish heart and pharyngeal endoderm.

The Drosophila homeobox gene tinman and its vertebrate homologs Nkx-2.5 and Nkx-2.3 are critical determinants of cardiac development. We report here the identification of a new tinman-related gene, nkx2.7, as well as orthologs of Nkx-2.5 and Nkx-2.3 in the zebrafish. Analysis of their expression in the developing zebrafish embryo reveals that nkx2.7 transcripts are the first to appear in cardiac mesodermal and pharyngeal endodermal precursors of the anterior hypoblast, anticipating both temporally and spatially the later expression of nkx2.5 and nkx2.3 in these lineages. The preeminence of nkx2.7 in these embryonic lineages is consistent with a key role in cell fate determination, perhaps in part through the induction of nkx2.5 and nkx2.3. The findings provide the first molecular clues as to the spatial organization of endodermal and cardiac mesodermal precursors in the zebrafish hypoblast immediately following gastrulation. They suggest a coordinate role for these three tinman-related genes in the development of the heart and pharyngeal arches, and reinforce the paradigm of gene duplication and subspecialization between Drosophila and vertebrate species. The results provide a framework in which to analyze potential changes in tinman-related gene expression during abnormal zebrafish development.

Amino Acid Sequence↗

Pregnancy management and outcomes in women with thalassaemia major.

The health background, management and outcomes of 25 pregnancies in 18 women with transfusion dependent beta thalassaemia are described with particular consideration of appropriate preconceptual guidance for such women. This is an observation study of women attending three collaborating London hospitals. Nine of the pregnancies required induction of ovulation. Two pregnancies were complicated by diabetes and three by hepatitis C. One patient was hepatitis B positive. Two pregnancies were in women with cardiac problems, one of whom died of cardiac failure nine months after delivery of a live child. Two of the pregnancies miscarried and three were terminated, with the others resulting in 21 live children (including one set of twins). 14 of the pregnancies were delivered by caesarean section. After pregnancy five women developed secondary amenorrhoea, two developed cardiac problems and two developed diabetes.

Abortion, Spontaneous↗

Decreases of calcium and phosphorus in monkey cardiac walls with development and aging.

To elucidate compositional changes of the cardiac walls with development and aging, the authors investigated changes of elements in the atrial and ventricular walls of monkeys. The left and right atrial walls, left and right ventricular walls, and interatrial and interventricular septa were resected from the subjects. The subjects consisted of 17 rhesus and 13 Japanese monkeys, ranging in age from 10 d to 33 yr. The element content of the cardiac walls was analyzed by inductively coupled plasma-atomic emission spectrometry. The Ca and P contents decreased in all of the left and right atrial and ventricular walls, interatrial septa, and interventricular septa with development, whereas the S and Mg contents decreased in the left and right ventricular walls with development. Regarding the relationships among elements, significant direct correlations were found among Ca, P, Mg, and Zn in all of the left and right atrial walls, left and right ventricular walls, and interatrial and interventricular septa, with some exceptions. As Ca decreased in the cardic walls, P, Mg, and Zn decreased simultaneously in the cardiac walls. The mass ratio of Ca/P decreased gradually with Ca decrease in both the atrial and ventricular walls, but it was not constant.

Aging↗

New real-time interactive cardiac magnetic resonance imaging system complements echocardiography.

OBJECTIVES: We conducted an initial clinical trial of a newly developed cardiac magnetic resonance imaging (CMRI) system. We evaluated left ventricular (LV) function in 85 patients to compare the clinical utility of the CMRI system with echocardiography, the current noninvasive gold standard. BACKGROUND: Conventional CMRI systems require cardiac-gating and respiratory compensation to synthesize a single image from data acquired over multiple cardiac cycles. In contrast, the new CMRI system allows continuous real-time dynamic acquisition and display of any scan plane at 16 images/s without the need for cardiac gating or breath-holding. METHODS: A conventional 1.5T Signa MRI Scanner (GE, Milwaukee, Wisconsin) was modified by the addition of an interactive workstation and a bus adapter. The new CMRI system underwent clinical trial by testing its ability to evaluate global and regional LV function. The first group (A) consisted of 31 patients with acceptable echocardiography image quality. The second group (B) consisted of 31 patients with suboptimal echocardiography image quality. The third group (C) consisted of 29 patients with severe lung disease or congenital cardiac malformation who frequently have suboptimal echo study. Two independent observers scored wall motion and image quality using the standard 16-segment model and rank-order analysis. RESULTS: CMRI evaluation was complete in less than 15 min. In group A, no significant difference was found between ECHO and CMRI studies (p = NS). In group B, adequate visualization of wall segments was obtained 38% of the time using ECHO and 97% of the time using CMRI (p < 0.0001). When grouped into coronary segments, adequate visualization of at least one segment occurred in 18 of 30 patients (60%) with ECHO and in all 30 patients (100%) with CMRI (p < 0.0001). In group C, adequate visualization of the wall segments was obtained in 58% (CI 0.53-0.62) of the time using echocardiography and 99.7% (CI 0.99-1.0) of the time using CMRI (p < 0.0001). CONCLUSIONS: The new CMRI system provides clinically reliable evaluation of LV function and complements suboptimal echocardiography. In comparison with the conventional CMRI, the new CMRI system significantly reduces scan time, patient discomfort and associated cost.

Adolescent↗

Neuregulins and neuregulin receptors in neural development.

The neuregulins are a family of closely related proteins that play important roles in neural and cardiac development, as well as in mammary carcinogenesis. The pleiotropic activities of these molecules are transduced by a set of receptor protein tyrosine kinases that exhibit structural similarity to the receptor for epidermal growth factor. Recent results have demonstrated essential roles for the neuregulins and their receptors in regulating cell number, determining cell fate, and establishing pattern in the developing central and peripheral nervous systems.

Animals↗

Cardiac tamponade from a fine silastic central venous catheter in a premature infant.

A 790 g infant developed cardiac tamponade 17 h after starting parenteral nutrition through a fine silastic catheter, the tip of which was accidentally positioned against the wall of the right atrium. Cold light examination suggested the diagnosis and pericardial aspiration of clear fluid with a high glucose content restored the circulation.

Cardiac Tamponade↗

Survival of 2 extreme preterm neonates with cardiac tamponade as a complication of percutaneous central venous catheterization.

We report 2 extreme preterm neonates who developed cardiac tamponade secondary to perforation of the myocardium by the percutaneous silastic central venous catheters, which were inserted for parental nutrition. Percutaneous pericardiocentesis was performed and pericardial effusion was aspirated, later proved by analysis to be total parental nutrition. The lines were removed and the patients successfully resuscitated and survived, both were sent home in good condition.

Cardiac Catheterization↗

Intrathecal morphine: one year's experience in cardiac surgical patients.

OBJECTIVES: This study was designed to assess the benefits and complications associated with the use of intrathecal morphine (ITM) in patients undergoing coronary artery bypass surgery (CABG). DESIGN: This was a retrospective chart review. SETTING: The study was performed in a single hospital that is affiliated with a university medical school. PARTICIPANTS: The charts of all patients who presented for CABG in a 12-month period were reviewed. INTERVENTIONS: All patients entered into the study had received ITM (0.03 mg/kg) at induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Complete data were available for 152 patients (86%). Median duration of ventilation postoperatively was 12 hours, and median duration of stay in the ICU was 72 hours. All patients received additional postoperative opioid analgesia, many by the epidural route. Fifteen percent developed respiratory complications, and the incidence of respiratory depression was 1.9%. Thirty-five percent required inotropic support; 17% percent were treated for hypertension; and 49% received antiarrhythmic therapy. The re-infarction rate was 2.6%, and 3% developed cardiac tamponade. Three patients developed neurologic complications unrelated to lumbar puncture. There were no in-hospital deaths. CONCLUSIONS: ITM is safe and provides effective pain relief after cardiac surgery. The high incidence of respiratory depression confirms the need for close observation of these patients postoperatively.

Aged↗

Effect of chronic renal failure on cardiac contractile function, calcium cycling, and gene expression of proteins important for calcium homeostasis in the rat.

Patients with chronic renal failure frequently develop cardiac hypertrophy and diastolic dysfunction; however, the mechanisms by which this occurs are still unclear. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy and studied for their isolated myocyte function, calcium cycling, and gene expression of proteins important in calcium homeostasis after 4 wk. Comparable rats subjected to suprarenal aortic banding for the same duration were used for comparison. Rats subjected to 5/6 nephrectomy and aortic banding developed comparable hypertension; however, rats subjected to 5/6 nephrectomy experienced a greater degree of cardiac hypertrophy and downregulation of cardiac sodium potassium ATPase (Na+/K+ -ATPase) activity than rats subjected to aortic banding. Moreover, cells isolated from the 5/6 nephrectomy rat hearts displayed impaired contractile function and altered calcium cycling compared with cells isolated from control or aortic constriction rat hearts. The 5/6 nephrectomy rat heart cells displayed a prolonged time constant for calcium recovery following stimulation, which corresponded to decreases in homogenate sarcoplasmic reticulum calcium ATPase-2a (SERCA2a) activity, protein density, and mRNA for SERCA2a. In conclusion, chronic renal failure leads to alterations in cardiac gene expression, which produces alterations in cardiac calcium cycling and contractile function. These changes cannot be explained only by the observed increases in BP.

Animals↗

Vertebrate model systems in the study of early heart development: Xenopus and zebrafish.

Xenopus and zebrafish serve as outstanding models in which to study vertebrate heart development. The embryos are transparent, allowing observation during organogenesis; they can be obtained in large numbers; and they are readily accessible to embryologic manipulation and microinjection of RNA, DNA, or protein. These embryos can live by diffusion for several days, allowing analysis of mutants or experimental treatments that perturb normal heart development. Xenopus embryos have been used to understand the induction of the cardiac field, the role of Nkx genes in cardiac development, and the role transforming growth factor beta molecules in the establishment and signaling of left-right axis information. Large-scale mutant screens in zebrafish and the development of transgenics in both Xenopus and zebrafish have accelerated the molecular identification of genes that regulate conserved steps in cardiovascular development.

Animals↗

Congenital heart disease in pregnancy: short- and long-term implications.

One hundred forty-four pregnancies that occurred in 74 patients with congenital heart disease at the Toronto General Hospital between 1975 and 1986 were reviewed. The patients were divided into two groups, those with acyanotic lesions and those with cyanotic lesions. Maternal and fetal outcomes in these two groups were compared. Patients with cyanotic lesions developed significantly more congestive heart failure and deteriorated more often in functional cardiac status than those with acyanotic lesions (p less than 0.005). Women with obstructive lesions had a higher incidence of pregnancy-induced hypertension than our general population (p less than 0.005). There was one maternal death in the puerperium in a woman with Eisenmenger's syndrome. Preterm births were more frequent in the cyanotic group (p less than 0.01) as were small for gestational age infants (p less than 0.005). In the cyanotic group the mean birth weight was 900 gm less than that in the acyanotic group (p less than 0.005). The major benefits of corrective cardiac surgery were in the cyanotic group and consisted of fewer spontaneous abortions (p less than 0.01) and small for gestational age infants (p less than 0.02) and more term births (p less than 0.01). Long-term follow-up revealed that 19.2% of women with acyanotic lesions had significant cardiac developments, compared with 90% in the cyanotic group (p less than 0.005). One of 87 infants (1.1%) had congenital heart disease and two had Marfan's syndrome.

Female↗

The use of microangiography in detecting aberrant vasculature in zebrafish embryos exposed to cadmium.

Embryonic vascular patterns in zebrafish (Danio rerio) could be visualised by confocal microscopy coupled with microinjected fluorescent microbeads. This microangiographic technique was adopted here, for the first time, to study the effects of cadmium on cardiovascular development in zebrafish embryos. Zebrafish embryos were incubated in culture medium containing 100 microM cadmium from 5 h post fertilisation (hpf) to 48 hpf. At 48 hpf, embryos were examined for viability and occurrence of malformations. The 100 microM cadmium caused 32.21 +/- 3.65% mortality and 20.33 +/- 4.04% visible malformations in surviving embryos. In the remaining embryos with no visible signs of malformations, further assessments for less obvious abnormalities were performed. Assessments on craniofacial development were made by digital measurements on areas of brains and eyes. Cardiac development was assessed by immunostaining the heart with the antibody MF20 specific for myosin heavy chain. Body lengths of the embryos were also measured. Embryonic development of brains, eyes, hearts and body lengths of visibly healthy embryos in the cadmium treatment group showed no significant difference from the controls. Embryonic vasculature of these visibly healthy embryos was then studied by microinjecting fluorescent microbeads of diameter 0.02 microm into the circulation. All the cadmium treated embryos showed localised vascular defects in the dorsal aortae, segmental and cranial vessels while none of the control embryos showed any aberrant patterns in the networking of the vasculature. Improved image analyses on the anterior regions revealed that cadmium treated embryos had markedly less complex networks of cranial vessels with fewer vessels perfusing the craniofacial regions. The number of branch points in the vascular network was counted. In untreated embryos, there were 135.6 +/- 51 branches in the vasculature in entire body. In the cadmium treated embryos, there were 64.5+/-31 branches. The difference was significant when assessed with Student's t-test. It appeared that although cadmium did not cause any signs of external malformations in these visibly healthy embryos, nonetheless induced impaired branching and anastomsis of the cranial vessels. This study revealed, for the first time, that vital vascular structures in fish embryos could be affected by exposure to cadmium. This technique allowed visualisation of vascular anomalies in embryos showing no external signs of malformations. The impairment of anatomical features during embryonic development might serve as meaningful health endpoints in ecotoxicological studies and in risk assessment.

Angiography↗

Cardiac arrest temperature: the effect of ethyl alcohol and carbon dioxide on baboons.

The effect of high inspired carbon dioxide concentrations and i.v. ethyl alcohol on the temperature at which cardiac arrest occurred was studied in chacma baboons. Alcohol-treated baboons developed cardiac arrest at a temperature of 24.3 degrees C (SD +/- 0.85) and control animals at 27 degrees C (SD +/- 1.30). There were no signs of cardiac failure before the occurrence of ventricular fibrillation.

Animals↗

Pressure overload per se rather than cardiac angiotensin converting enzyme activity may be important in the development of rat cardiac hypertrophy.

OBJECTIVE: To investigate the roles of the renin-angiotensin system and blood pressure in cardiac hypertrophy caused by a pressure overload. METHODS: Cardiac hypertrophy was induced by constricting the abdominal aorta above the renal arteries. After they had been banded, the rats were treated with the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of quinapril [an angiotensin converting enzyme (ACE) inhibitor], or the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of TCV-116 [an angiotensin II (AngII) AT1 receptor antagonist], for 4 weeks. Then, we measured the mean blood pressure (MBP), body weight, left ventricular weight (LVW), and serum and cardiac ACE activities. RESULTS: The higher dose of quinapril and that of TCV-116 prevented left ventricular hypertrophy and MBP elevation. Both the higher and the lower doses of quinapril reduced the serum and cardiac ACE activities significantly, whereas the higher dose of TCV-116 reduced the cardiac ACE activity and increased the serum ACE activity. The lower dose of quinapril, however, exerted no significant effect on MBP and the LVW:body weight ratio, although it reduced the cardiac and serum ACE activities significantly. There was a significant positive correlation between the MBP and the LVW:body weight ratio regardless of the cardiac ACE activity in data from all groups (r = 0.676, P < 0.0001). CONCLUSIONS: Our data indicate the importance of the blood pressure as a determinant of cardiac hypertrophy because inhibition of cardiac ACE activity alone without lowering of the blood pressure is insufficient to prevent cardiac hypertrophy. Our results suggest the presence of other pathways for AngII production not mediated by ACE, or growth factors other than AngII in pressure-overload cardiac hypertrophy.

Angiotensin Receptor Antagonists↗