Association of prolidase activity, oxidative parameters, and presence of atrial fibrillation in patients with mitral stenosis.

BACKGROUND: Mitral stenosis (MS) is a common cause of atrial fibrillation (AF). Oxidative stress and inflammation factors were shown to be involved in atrial remodeling. The study aim was to compare the oxidative parameters and prolidase activity in severe MS patients with and without AF. METHODS: The study population was comprised of 33 patients with MS and sinus rhythm (group I), 27 patients with MS and AF (group II), and 25 healthy controls (group III). Plasma prolidase activity, total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) were determined. Additionally, we measured tissue TOS and TAC in patients with mitral valve replacement. RESULTS: TAC and OSI were higher, but TOS and prolidase were lower in patients with MS than control (all p <0.001). These parameters were similar in group I and group II (ANOVA p >0.05). Tissue TAC was significantly lower in group II than group I (0.015 +/- 0.01 vs. 0.026 +/- 0.01 mmol Trolox equiv/L, p = 0.014), tissue TOS was similar between groups I and II (0.24 +/- 0.06 vs. 0.22 +/- 0.05 mmol Trolox equiv/L, p = 0.161). Presence of AF was correlated with systolic blood pressure, left atrial diameter, plasma TAC, tissue TAC, plasma TOS, plasma OSI, and plasma prolidase activity. Tissue TAC level (beta = -0.435, p = 0.006) and left atrial diameter (beta = 0.460, p = 0.003) were independently related with presence of AF in patients with MS. CONCLUSIONS: This study suggested that the presence of AF in patients with severe MS may be associated with the plasma prolidase activity, tissue and plasma oxidative parameters.

Peripheral blood levels of matrix metalloproteinases in patients referred for percutaneous balloon mitral valve commissurotomy.

BACKGROUND AND AIM OF THE STUDY: Inflammation may play a central role in the progression of stenotic valvular heart disease. Serum levels of matrix metalloproteinases (MMPs), markers of extracellular matrix (ECM) turnover and potential markers of active inflammation, have been recently demonstrated in several inflammatory processes. The present study was designed to examine whether systemic evidence of ECM turnover was present in advanced stenotic mitral valve disease. METHODS: Serum levels of MMP-1, -3 and -9 were measured in 114 patients with mitral stenosis referred for percutaneous balloon mitral valve commissurotomy, and compared to those in 48 healthy, age- and gender-matched controls. RESULTS: Serum levels of MMP-1, -3 and -9 did not vary according to hemodynamic profile or heart failure class at the time of blood sampling. Levels of MMP-1 and -3 were not significantly different between those patients with mitral stenosis and controls. The level of MMP-9 was significantly higher in patients with mitral stenosis than in controls, and did not appear to be altered by commissurotomy. CONCLUSION: Serum levels of MMP-9 were elevated in patients with mitral stenosis, providing further evidence that inflammation and ECM remodeling plays an important role in the pathophysiology of valvular heart disease.

[Study on the total activity of PKC and the quantity of PKC (alpha, beta) in left auricle tissues of the patients with mitral disease and atrial fibrillation].

OBJECTIVE: To investigate the possible relation of atrial fibrillation (AF) with the total activity of protein kinase C (PKC) and the quantity of PKC (alpha, beta) in the left auricle tissues of the patients with mitral disease. METHODS: Thirty-five patients hospitalized for valve replacement surgery were divided into four groups: group A (simple mitral stenosis with AF), group B(simple mitral stenosis with sinus rhythm), group C(simple mitral regurgitation with AF), group D (simple mitral regurgitation with sinus rhythm), The total PKC, activity and the quantity of PKC alpha and PKC beta were measured and compared in an attempt to find out whether significant difference exists between the groups. RESULTS: There was no significant difference in total PKC activity between the four groups (P > 0.05). The quantity of PKC alpha in patients with AF was lower than that in patients with sinus rhythm, the quantity of PKC beta in patients with AF was higher than in patients with sinus rhythm. But these differences were not statistically significant (P > 0.05). CONCLUSION: Under conditions of the same rhythm and the same heart disease, the total PKC activity and the quantity of PKC (alpha, beta) of the four groups showed no significant difference. No obvious relation was seen between the total activity of PKC in left auricle tissue and the occurrence of AF in patients with mitral disease, but more research on the relation between AF and the quantity of PKC isoforms in left auricle tissues would be needed.

Nitric oxide synthase expression in lungs of pulmonary hypertensive patients with heart disease.

Since little is known about the contribution of endothelial nitric oxide synthase (e-NOS) to the mechanism of pulmonary vasospasm and the development of pulmonary vascular occlusive disease, we elucidate how e-NOS is expressed in lung biopsy specimens obtained from operative patients with pulmonary hypertension. Lung biopsy specimens were obtained from 17 patients who underwent open-heart operations for various heart diseases. A piece of normal lung specimen was also obtained from the resected lungs of three lung cancer patients as a control. e-NOS expression was visualized with a monoclonal antibody against e-NOS, and the level of expression was partially quantified. Significantly high levels of e-NOS expression were seen in adult patients, whose preoperative mean pulmonary arterial pressures were greater than 20 mm Hg. In contrast, e-NOS expression in pediatric patients with the same levels of mean pulmonary arterial pressure was the same as that in the controls and in low pulmonary arterial pressure. There was a statistically significant positive correlation between the level of e-NOS expression and Heath--Edwards grading. These data suggest that the e-NOS expression in lung tissue is induced when pulmonary vascular obstructive diseases progress.

Manganese-containing superoxide dismutase in blood and urine during open-heart surgery.

Concentrations of Manganese-containing superoxide dismutase (Mn-SOD) were measured perioperatively by enzyme immunoassay in serial samples of arterial and coronary sinus blood and urine taken from 18 patients undergoing mitral valve surgery. The mean Mn-SOD concentration in the arterial blood samples was 66.2 (SD 16.1 ng/ml) at induction of anesthesia, increased gradually after reperfusion and peaked on the 2nd post-operative day [150 (SD 58.3) ng/ml]. The mean concentration of Mn-SOD in the coronary sinus blood samples was significantly higher than in the arterial samples only at the 6th hour after reperfusion [97 (SD 21.8) ng/ml vs 90.3 (SD 20.9) ng/ml, p < 0.05]. Although concentrations of Mn-SOD in blood did not increase in 8 patients who underwent midline sternotomy for a mediastinal tumor, they increased dramatically in 3 patients who sustained a perioperative myocardial infarction. During open heart surgery the peak values of plasma Mn-SOD concentrations were correlated to that of plasma creatine kinase-MB concentrations (r = 0.5532, n = 18, p < 05) and cardiac ischemic period (r = 0.5186, n = 18, p < 05). Although the meaning of an increase in plasma Mn-SOD concentrations during open heart surgery is not clarified, it may be released from the heart and anywhere also in the body damaged during cardiopulmonary bypass.

S-adenosylhomocysteine hydrolase activity in human myocardium.

OBJECTIVE: Measurement of S-adenosylhomocysteine (SAH) accumulation in the heart reflects the concentration of free cytosolic adenosine and is thus a sensitive indicator of regional myocardial ischaemia. To evaluate the possibility of applying this method in combination with 11C-SAH positron emission tomography (PET) to patients with ischaemic heart disease the activity of SAH hydrolase in human heart muscle and its regional distribution were studied. METHODS: Myocardium from patients with dilated cardiomyopathy (n = 4), hypertrophic obstructive cardiomyopathy (HOCM, n = 6), and mitral stenosis (n = 3) was analysed. Additional studies were performed in myocardium, isolated cardiomyocytes, and endothelial cells from dog and guinea pig hearts. Enzyme activity in synthetic and hydrolytic direction including kinetic data (Vmax, KM values, pH dependency) was measured in the cytosolic fraction of myocardial tissue and cell extracts, using high performance liquid chromatography and photometric methods, respectively. RESULTS: Rates of SAH synthesis (Vmax) in the left ventricle in dilated cardiomyopathy, mitral stenosis, and HOCM were 0.8 (SEM 0.1), 1.0(0.2), and 1.7(0.1) nmol.min-1.mg-1 protein respectively. KM values for DL-homocysteine, adenosine, and SAH in HOCM were 187, 2.2, and 3.4 microM, respectively. Enzyme activity was homogeneously distributed among right and left atria, right and left ventricles, and septum. Additional studies in homogenated muscle and isolated cardiomyocytes of guinea pig and canine hearts showed activities similar to man. CONCLUSIONS: (1) SAH hydrolase activity in the human heart is quantitatively comparable to that found in other mammals but certain myocardial diseases may go along with changes in SAH hydrolase activity; (2) the kinetic properties, absolute amounts, and homogeneous distribution of the enzyme may permit the non-invasive determination of free adenosine in the human heart by PET.

Coenzyme Q10 and key enzyme activities in papillary muscle related to left ventricle function in mitral valve disease.

Coenzyme Q10 (CoQ10) was studied in papillary muscle from 18 patients (52-67 years, 2 females) subjected to open heart surgery due to mitral valve disease. In addition the enzyme activities of lactate dehydrogenase (LD) with its five isozymes, citrate synthase (CS) and mitochondrial CK (CK-MIT) were determined. Myocardial function was assessed by means of left ventricle (LV) angiography. CoQ10 averaged 0.39 (range 0.26-0.59) micrograms x mg-1 dw. On an individual basis CoQ10 was related to CS activity although not as closely as CK-MIT (r = 0.45, p less than 0.05 versus r = 0.86, p less than 0.001). The ratio (CoQ10) x (CS activity)-1 was calculated to represent mitochondrial quality. The level of LD3 fraction increase was used to mark for the degree of metabolic stress in the heart. LD3 fraction was negatively related to the quality index (r = -0.71, p less than 0.001). Thus, those with a low CoQ10 per unit of CS activity had also a high LD3 isozyme fraction. In a subset of 12 patients with isolated mitral regurgitation due to myxomatous valve degeneration, CoQ10 and the ratio CoQ10 over CS decreased with the degree of LV function impairment (r = -0.58, p less than 0.05 and r = -0.68, p less than 0.05, respectively). The quality index takes into account not only enzyme activity but also the potential for control of free oxygen radicals.

Myocardial enzyme activities in patients with mitral regurgitation or mitral stenosis.

To determine the adaption of myocardial metabolism in mitral regurgitation and mitral stenosis, human papillary muscles obtained during open heart surgery were analysed to measure selective enzyme activities in energy metabolism. All enzyme activities were expressed per unit dry weight muscle, per unit alkali soluble protein, and per unit total creatine and the different results compared. The activities of enzymes concerned with mitochondrial energy production and energy transfer (namely, citrate synthase and mitochondrial creatine kinase) tended to be higher in papillary muscles from hearts with mitral regurgitation than in those with mitral stenosis. The activities of enzymes concerned with cytoplasmic energy production (creatine kinase MM, lactate dehydrogenase, and phosphofructokinase) did not show statistically significant differences between mitral regurgitation and mitral stenosis. The ratio of creatine kinase MB activity to total creatine content showed the greatest difference when papillary muscles from patients with mitral regurgitation and mitral stenosis were compared (31% higher in mitral regurgitation; p less than 0.001). The specific function of creatine kinase MB, which is located in cytoplasm, is not well defined. Creatine kinase MB activity increases with extreme endurance training of human skeletal muscle. Thus the higher creatine kinase MB activity in papillary muscle of mitral regurgitation may represent an adaptation to increased physical demand.

Myosin isoenzyme distribution in overloaded human atrial tissue.

Using nondenaturing polyacrylamide gel electrophoresis, we have identified two distinct myosin isoenzymes in human atrial tissue that correspond to the V1 and V3 isomyosins found in rat ventricular tissue. Normal left and right atrial appendages have approximately 50% V3. When the left atrium was exposed to hemodynamic overload secondary to mitral stenosis, the percent V3 increased to 77 +/- 10% (n = 10); exposure to hemodynamic overload secondary to mitral regurgitation caused an increase to 70 +/- 14% (n = 6). Changes in the isoenzyme pattern were seen in the right atria of patients with mitral stenosis and markedly elevated pulmonary arterial pressures compared with control subjects and patients with mitral stenosis without severe pulmonary hypertension. Several clinical variables were examined to determine which factors might influence isoenzyme expression. Age, sex, the presence of atrial fibrillation, and pulmonary capillary wedge pressure did not predict the isoenzyme pattern. However, patients with mitral valvular disease and only slightly enlarged left atria tended to have a higher percent V3 than those with massively enlarged atria. These data confirm that human atrial tissue, like rat ventricular tissue, can alter its isomyosin composition in response to a hemodynamic load. The data further suggest that the isoenzyme shift is an early adaptation to the imposed load.

Relationship between the myofibrillar ATPase activity of human biopsy material and hemodynamic parameters.

The myofibrillar ATPase activity and pyrophosphate gel electrophoretic pattern of native myosin of fresh human left ventricular papillary muscles were examined in 52 cases of mitral valve replacement. The myofibrillar ATPase activity of hypertrophied myocardium did not differ from that of non-hypertrophied myocardium (mean +/- SD, 36.2 +/- 8.7 vs 31.8 +/- 8.6 nmolPi/mg/min, ns) and there was no significant difference in myofibrillar ATPase activity as a function of left ventricular enddiastolic pressure. Pyrophosphate gel electrophoresis of myosin revealed the presence of two components. It is questionable whether the component of higher electrophoretic mobility (approximately 25-35% in concentration) is identical with rat ventricular myosin VM-1 because an increase in this component seems to correlate with a decrease of myofibrillar ATPase activity, its concentration was significantly higher in the hearts with left ventricular hypertrophy, high enddiastolic pressure, high aortic pressure or low cardiac index. From these results, it is not necessarily clear whether hemodynamic overload in valvular heart diseases can alter left ventricular myofibrillar ATPase activity, but it can be said that the overload influences the concentration of the two components of native myosin revealed by pyrophosphate gel electrophoresis.

Effects of adenosine on transmembrane potential and sarcolemmal Na+-K+ ATPase activity of human atrial myocardium.

Adenosine effects on the transmembrane potential characteristics and the sarcolemmal Na+-K+ ATPase activity of human atrial myocardium were studied in tissue from 20 patients who were divided into 2 groups based on the maximum diastolic potentials (MDP) greater than or less than -60 mV. Group A consisted of 10 patients with MDP of 70.84 +/- 4.20 mV and Na+-K+ ATPase activity of 15.37 +/- 0.46 mumole Pi/mg/hr. Ten patients with MDP of 44.54 +/- 6.24 mV and Na+-K+ ATPase activity of 12.55 +/- 0.42 mumole Pi/mg/hr were included in group B. Adenosine had no effects on the electrophysiological properties and the sarcolemmal Na+-K+ ATPase activity of atrial myocardium at concentrations below 1 X 10(-5) M in either group. Adenosine resulted in mildly altered atrial transmembranes potentials without significant effect on Na+-K+ ATPase activity at concentrations between 1 X 10(-5) M and 5 X 10(-4) M. However, a significant reduction of transmembrane potentials and an apparent inhibition of Na+-K+ ATPase activity were observed only in tissue from group B. These results suggest that: 1) adenosine has no effect on the electrophysiological properties and the sarcolemmal Na+-K+ ATPase activity of human atrial myocardium at physiological concentrations; 2) adenosine induced inhibition of the sarcolemmal Na+-K+ ATPase activity in slow channel-dependent atrial tissues may be a mechanism responsible for the alterations of transmembrane potentials under unphysiological conditions; and 3) adenosine contributes to the genesis of cardiac arrhythmias during acute myocardial ischemia, which can reduce transmembrane potentials of the myocardial cells and may increase the myocardial adenosine level above its effective concentration.

Five creatine kinase isoenzymes in serum of a patient with severe heart disease.

Abnormal creatine kinase (CK) isoenzyme patterns were observed in the serum of a 64-year-old woman with severe heart disease. Agarose electrophoresis revealed the presence of all the usual CK isoenzymes (MM, MB, and BB) plus an extra band between MM and MB. Total serum CK activity was within the normal range. Within 2 h after the patient suffered cardiorespiratory arrest, a fifth CK isoenzyme appeared, cathodal to MM. After cardiac valve replacement, the patient's serum showed a high activity of CK, but the isoenzyme pattern showed only MM and, transiently, an MB band. With return of the serum CK activity to normal, the CK isoenzymes pattern also became normal, virtually ruling out genetic variant(s). The abnormal CK isoenzyme patterns might have been the consequence of severe hypoxemia in the patient, thus such patients may represent an ominous prognostic sign. The association of the abnormal pattern upon admission with rapid deterioration of the condition of the patient suggests prompt attention for the prevention of complications.

[Lactae dehydrogenase activity and its isoenzymatic spectrum in the myocardium in rheumatic heart defects]. / Aktivnost' laktatdegidrogenay i ee izofermentnyi spektr v miokarde bol'nykh revmaticheskimi porokami serdtsa.

The activity of lactate dehydrogenase (LDH) and its isoenzymatic spectrum were studied in biopsy specimen of the myocardium of 35 patients with mitral valvular disease who underwent operation. Starch gel electrophoresis was used. Four fractions of LDH isoenzymes were detected: LDH1, LDH2, LDH3, and LDH4. A definite metabolic trend of their changes in different stages of the disease was determined. LDH1 activity was considerably increased in patients with stage III mitral stenosis who had complications in the postoperative period. This is evidence of unstable compensation in patients of this group and may indicate the possible development of complications in the early postoperative period.

[Activity of enzymes of pentosephosphate pathway in the erythrocytes, myocardium and intercostal muscle of patients with mitral valve stenosis]. / Aktivnost' fermentov pentozofosfatnogo puti v eritrotsitakh, miokarde i mezhrebernoi myshtse bol'nykh mitral'nym stenozom

Decrease in activities of glucose-6-phosphate dehydrogenase and transketolase was observed in erythrocytes of patients with mitral stenosis. Development of the disease was accompanied by a further decrease in the enzymatic activity. The activity of the enzymes was increased in myocardium of atrium sinistrum at the IV stadium as compared with the III stadium of the disease. The glucose-6-phosphate dehydrogenase activity was decreased and the transketolase activity was unaltered in intercostal muscle of the patients.