Leukocyte expression of heme oxygenase-1 [hmox1] varies inversely with severity of tricuspid regurgitation in acute pulmonary embolism.

OBJECTIVE: Pulmonary embolism (PE) can cause intracardiac hemolysis and increased plasma hemoglobin and arginase-1, which can worsen pulmonary vasoconstriction. We test the hypothesis that patients with PE that causes tricuspid regurgitation (TR), indicative of higher pulmonary arterial pressures, have decreased leukocyte expression of hmox-1 compared with patients with PE and no TR and patients without PE. DESIGN: Prospective, noninterventional study. PATIENTS: Normotensive patients with suspected PE (n=87) who underwent CT pulmonary angiography and transthoracic Doppler-echocardiography. MEASUREMENTS: Significant TR was defined as a jet velocity >2.7m/s. Leukocyte expression of hmox-1, haptoglobin, haptoglobin related gene, the haptoglobin receptor, CD163 and cox-2 genes were assessed by quantitative rtPCR, and the hmox-1 promoter was examined for the -413 A→T SNP and GT repeat polymorphisms. RESULTS: Of the 44 (50%) with PE+, 22 had TR+, and their mean pulmonary vascular occlusion (39±32%) did not differ significantly from patients who were TR- (28±26%, P=0.15). Patients with PE+ and TR+ had significantly lower expression of hmox-1 and haptoglobin genes than patients without PE+ and no TR. Expression of hmox-1 varied inversely with TR velocity (r(2)=0.45, P<0.001) for PE+ (n=22) but not patients without PE. Hmox-1 expression did not vary significantly with genotype. Cox-2 did not differ between groups and had no correlation with TR. CONCLUSIONS: Severity of TR varied inversely with hmox-1 expression, suggesting that hmox-1 expression affects pulmonary vascular reactivity after PE.

Influence of angiotensin-converting enzyme gene insertion/deletion polymorphism on rheumatic valve involvement, valve severity and subsequent valve calcification.

BACKGROUND AND AIM OF THE STUDY: The relationship between the severity of chronic rheumatic heart disease (RHD) and predisposing factors is unknown, and genetic predictors for severe scarring and calcification of the mitral valve are not well defined. A high angiotensin-converting enzyme (ACE) activity has been demonstrated in valve tissue. Thus, a case-control study was conducted to investigate any possible relationship between ACE gene polymorphisms and chronic mitral valve disease severity and calcification. METHODS: This case-control study included 82 patients (24 males, 58 females; mean age 40.3 +/- 14.7 years) with chronic rheumatic mitral valve, and 154 control subjects (53 males, 101 females; mean age 43.4 +/- 13.4 years). ACE gene insertion/deletion (I/D) polymorphisms were identified using polymerase chain reaction methods. RESULTS: Among RHD subjects, 31 (30.6%) were D/D, 25 (32.7%) were I/D, and 26 (18.8%) were I/I. Among controls, 57 (57.4%) were D/D, 69 (61.3%) were I/D, and 28 (35.2%) were I/I. The frequency of ACE I/I genotype was higher in RHD subjects than in controls (chi2 = 7.4, df = 2, p < 0.030; D/D versus I/D versus I/I), or (chi2 = 5.5, df = 1, p < 0.019; DD + ID versus II). Predisposition to RHD was significantly less frequent in the D/D genotype. There was no statistically significant difference in the genetic analysis of RHD with respect to mitral valve score, severity of mitral regurgitation and left atrial diameter. Mitral valve calcification was significantly associated with a higher frequency of I/I genotype and I/D genotype than D/D genotype alone (chi2 = 6.2, df = 2, p = 0.043). The ACE I/I genotype was associated with a predisposition to a greater risk of severe calcific valve disease. CONCLUSION: The ACE I/I genotype is more common in patients with rheumatic valve disease than in the normal population. This suggests that the ACE gene polymorphism may be involved in the pathogenesis of rheumatic heart disease.

Duplex Doppler sonography of the hepatic vein in tricuspid regurgitation.

Patients with tricuspid regurgitation may present initially with vague abdominal symptoms and elevated liver enzymes. In the absence of diagnostic sonographic findings, patients may be subjected to an unnecessary invasive liver biopsy for an accurate diagnosis. We recently described the association of the pulsatile portal venous waveform on duplex Doppler sonography with tricuspid regurgitation in 15 patients. In this study I describe the changes in the hepatic venous waveform in these patients and compare the findings with the final diagnosis as determined by Doppler echocardiography (n = 14) or ultrafast CT (n = 1). All patients had clinical findings consistent with liver dysfunction and were referred for sonography to rule out diseases of the liver, biliary tree, or hepatic or portal veins. All patients had persistently dilated hepatic veins and inferior venae cavae. Twenty-four volunteers, 11 of whom had simultaneous ECG tracings, served as a control group. The main findings on the hepatic duplex sonogram in the disease group were a decrease in the size of the antegrade systolic wave with a systolic/diastolic flow velocity ratio of less than 0.6 (n = 4) or reversal of the systolic wave (n = 10). In all volunteers, systolic flow was antegrade and the ratio was more than 0.6. Two diagnoses were false positive and one was false negative. In some patients with sonographic signs of congestive heart failure, duplex Doppler sonography of the hepatic vein may be helpful in the diagnosis of one of the causes of liver dysfunction, tricuspid regurgitation.

[Secondary tricuspid insufficiency and right atrial myosin ATPase activity].

Myosin of heart muscle shows ATPase activity. In the atrial myocardium, normal isozymic pattern was alpha dominant which converted to being beta dominant in an overloaded hypertrophy. In order to clarify the distribution of myosin isozymes in human heart, ATPase activity of the atrial myosin recovered from the patient underwent open heart surgery was determined. In the present study, ATPase activity of right atrial myosin from the heart with tricuspid regurgitation (TR) (group A (n = 6); 398.1 +/- 67.0 nmol pi/mg/min) was significantly less than that from the heart without TR (group B (N = 7); 533.9 +/- 62.4, p less than 0.05). The myosin ATPase activity showed correlation with systemic RA pressure (y = 0.019x + 19.6, r = -0.68429), systemic RV pressure (y = 0.039x + 58.67, r = 0.73484), SVI (y = 0.05x + 18.1, r = 0.87587) and RV maxDp/Dt (y = 0.42x + 589.9, r = -0.67493) (p less than 0.05). These data suggests that preoperative cardiac function involves in cardiomuscular structure with redistribution of contractile protein.

Differences in response of myosin isozyme transition of ordinary and specialized myocardium to overload.

To investigate the response of myosin isozyme transition in specialized myocardium to cardiac overload, we examined immunohistochemically the distribution of myosin isozymes in sinus node cells of overloaded canine atria, using the monoclonal antibodies CMA19 and HMC14, which are specific for atrial myosin heavy chain (alpha-HC) and ventricular myosin heavy chain (beta-HC), respectively. Overloading in canine right atria was induced by artificial tricuspid valve regurgitation and pulmonary stenosis. Right atrial mean pressure rose to 15-20 mm Hg (n = 4) 2 months after surgery. In the working myocardium, cardiac overload caused redistribution of myosin isozymes, alpha-HC to beta-HC. Compared with the normal right atria, fewer myocytes were labeled with CMA19, but more were labeled with HMC14. However, the reactivity of sinus node cells with CMA19 and HMC14 was not changed between normal and overloaded right atria, indicating no redistribution of myosin heavy chain isozymes, alpha-HC to beta-HC. These results suggest that isozymes in myosin heavy chains in the specialized myocardium are protected from overload effects by their firm cytoskeletal framework or other mechanisms.

Neurochemical indices of autonomic innervation of heart in different experimental models of heart failure.

Parasympathetic neural regulation of the failing heart is impaired. In order to investigate parasympathetic mechanisms in experimental heart failure, measurements were made of choline acetyltransferase (CAT) activity and [3H]-quinuclidinyl benzilate (QNB) binding in hearts of 1) hamsters with skeletal and cardiac myopathy, 2) dogs with pulmonary artery constriction and tricuspid avulsion, and 3) guinea pigs with pulmonary artery constriction. Tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities and norepinephrine levels served as indices of sympathetic innervation. In myopathic hearts, total CAT activity decreased (P less than 0.05) compared to age-matched controls. In canine and guinea pig right heart failure, total CAT activity was normal in contractile and specialized tissues. Alterations in [3H]-QNB binding paralleled CAT activity being decreased (P less than 0.05) only in myopathic hearts. In all three models, indices of sympathetic innervation were altered in ways qualitatively different from parasympathetic indices; TH and DBH activities were increased (P less than 0.05) in myopathic ventricles, decreased (P less than 0.05) in hypertrophied canine and guinea pig ventricles and non-hypertrophied canine ventricles, and normal in non-hypertrophied guinea pig ventricles. These results indicate that alterations in cardiac parasympathetic indices vary depending on the etiology of heart diseases and differ qualitatively from alterations in sympathetic indices. Selective determinants are necessary to explain the varied changes.