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We determined the acute effects of the angiotension converting enzyme inhibitor captopril on the arterial mechanics in rats at different ages, based on the exponentially tapered T-tube model. Male Wistar-Kyoto rats aged 4 and 12 months were individually referred to as young (n = 8) and adult rats (n = 8) and were anesthetized and thoractomized. The pulsatile aortic pressure and flow signals before and after the administration of captopril (20 mg/kg, i.p.) were measured by a high-fidelity pressure sensor and an electromagnetic flow probe, respectively. In each age group, captopril showed little change in basal heart rate as well as cardiac output. However, captopril produced a drop of 15% in mean aortic pressure in young and a fall of 12% in adult rats. In addition. captopril reduced total peripheral resistance by 21% in young and by 23% in adult animals. As for the pulsatile nature of the arterial system, captopril had increased wave transit time of the lower body circulation of 10% in young and of 12% in adult rats. By contrast, captopril reduced wave reflection factor by 22% in young and by 25% in adult animals. In conclusion, the converting enzyme inhibitor captopril has a stiffness-decreasing effect on Windkessel vessels and a dilated effect on resistance arterioles in either young or adult rats. No age dependence of vascular response and reflex tachycardia to captopril has been found in rats between 4 and 12 months.

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease involving both the upper and lower motor neurons in the brain stem and spinal cord. Although it is well known that various central nervous system disorders can produce a 'pseudo-infarction' pattern on the electrocardiogram, there have been no reports of this particular pattern in ALS patients. This report concerns an ALS patient who presented with an ECG pattern of S-T elevation followed by biphasic T and inverted T without any detectable myocardial abnormality. Data from the present case suggest that this pattern may be an inherent characteristic of ALS.

Desmin filaments are muscle-specific intermediate filaments located at the periphery of the Z-discs, and they have been postulated to play a critical role in the lateral registration of myofibrils. Previous studies suggest that intermediate filaments may be involved in titin assembly during the early stages of myofibrillogenesis. In order to investigate the putative function of desmin filaments in myofibrillogenesis, rabbit anti-desmin antibodies were introduced into cultured cardiomyocytes by electroporation to perturb the normal function of desmin filaments. Changes in the assembly of several sarcomeric proteins were examined by immunofluorescence. In cardiomyocytes incorporated with normal rabbit serum, staining for alpha-actinin and muscle actin displayed the typical Z-line and I-band patterns, respectively, while staining for titin with monoclonal anti-titin A12 antibody, which labels a titin epitope at the A-I junction, showed the periodic doublet staining pattern. Staining for C-protein gave an amorphous pattern in early cultures and identified A-band doublets in older cultures. In contrast, in cardiomyocytes incorporated with anti-desmin antibodies, alpha-actinin was found in disoriented Z-discs and the myofibrils became fragmented, forming mini-sarcomeres. In addition, titin was not organized into the typical A-band doublet, but appeared to be aggregated. Muscle actin staining was especially weak and appeared in tiny clusters. Moreover, in all ages of cardiomyocytes tested, C-protein remained in the disassembled form. The present data suggest the essential role of desmin in myofibril assembly.

Genetic and environmental factors may contribute to the pathogenesis of essential hypertension. To facilitate genetic studies of hypertension and renal disorders, we sought to clone novel genes from a modified, equalized kidney (MEK) cDNA library of a spontaneously hypertensive rat (SHR).A kidney cDNA library of an SHR was synthesized using the modified equalization method. Inserts of 350 random clones were amplified by polymerase chain reaction (PCR) and sequenced, of which 246 were presumably unknown after being compared against a nonredundant database in the GenBank. The cDNA ends of clone 38S were obtained by rapid amplification of cDNA ends, sequenced, and then analyzed with Translate, Prosite, Profile, SignalP, and TMpred programs.The full-length cDNA was 938 bp, and translated into a 182-amino acid protein. The deduced protein had a metallophosphoesterase domain, a signal peptide at its amino end, a protein kinase C phosphorylation site, and a transmembrane domain. Northern blot analysis revealed that this gene was expressed in the heart, brain, spleen, lungs, liver, skeletal muscles, kidneys and testes of Sprague-Dawley rats. A putative protein of Arabidopsis thaliana shares 62% homology with protein 38S, but the two proteins differ in terms of function and structure.Our results support that protein 38S is a novel membrane metallophosphoesterase, although its function in the kidneys remains to be elucidated. This study also demonstrates the feasibility of using PCR to clone novel genes from our MEK cDNA library.

N-cadherin is a member of the Ca(2+)-dependent cell adhesion molecules and plays an important role in the assembly of the adherens junction in chicken cardiomyocytes. In addition to being present at the cell-cell junction, N-cadherin is associated with costameres in extrajunctional regions. The significance of the N-cadherin-associated costameres and whether catenins are components of costameres in chicken cardiomyocytes are not known. In this study, double-labeling immunofluorescence microscopy was used to determine the extrajunctional distribution of both N-cadherin and its cytoplasmic associated proteins, alpha- and beta-catenins, and their relationship to myofibrillar Z-disc alpha-actinin. N-cadherin, alpha-, and beta-catenins were all found to be present at the extrajunctional region and, in some cases, were codistributed with myofibrillar alpha-actinin exhibiting a periodic staining pattern. Confocal microscopy confirmed that both N-cadherin and beta-catenin colocalized with peripheral myofibrillar alpha-actinin on the dorsal surface of cardiomyocytes as components of the costameres. Intracellular application of antibodies specific for the cytoplasmic portions of N-cadherin, alpha-, and beta-catenin, either by electroporation or microinjection, resulted in myofibril disorganization and disassembly. These results suggest the existence of N-cadherin/catenin-based costameres in the dorsal surface of cultured chicken cardiomyocytes in addition to the integrin/vinculin-based costameres found in the ventral surface and indicate that the former set of costameres is essential for cardiac myofibrillogenesis.

During early ventricular depolarization, the normal body surface potential map (BSPM) has a maximal potential that is greater than the absolute value of the minimal potential; this reverses in late depolarization, so that the absolute value of the minimal potential is greater. Nevertheless, an abnormal "early reversal" BSPM pattern has been observed in some patients with cardiovascular disease. To investigate the implications of this abnormal pattern, BSPMs were studied in 100 patients with angiographically proven coronary artery disease (CAD). There were 57 patients (57%; group A) with an abnormal early reversal pattern and 43 (43%; group B) without this early reversal pattern. A significant (70% narrowing) CAD lesion was observed in a significantly higher proportion of group A (97%) than group B (77%) patients, although the number of involved coronary arteries was not significantly different between the two groups. The maximal extent of the abnormal negative potential was significantly greater in group A (21.2 +/- 9.6 cm2) than in group B (12.2 +/- 7.5 cm2). The abnormal negative potential lasted significantly longer in group A (22.1 +/- 12.1 msec) than in group B (14.4 +/- 9.2 msec). Similarly, the minimal potential lasted significantly longer in group A (20.1 +/- 11.3 msec) than in group B (11.8 +/- 7.1 msec). These findings suggest that the abnormal early reversal BSPM pattern is a valuable indicator of extensive myocardial lesions and the severity of CAD.

We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation.Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear.A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase.The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation.L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

A rat polyclonal anti-M-line protein antiserum and three mouse monoclonal anti-titin antibodies (E2, F3, and A12) were used to study the spatiotemporal relationship between M-line proteins and titin during myofibril assembly in cultured chicken cardiomyocytes by immunofluorescence microscopy. In day 2 cultures, M-line proteins and titin were detected as punctate staining in most cardiomyocytes, which possessed many nonstriated fibrils. At a late stage (day 3 cultures), M-line proteins were incorporated into dot-like structures along nonstriated fibrils, while titin staining was continuous on these structures. As development progressed, M-line proteins were registered in periodic pattern in the mid-A band. In cardiomyocytes from day 5 cultures, the titin bands were separated by an unstained region, and achieved their adult doublet pattern. Thus, the organization of titin in the sarcomere appears to occur later than that of M-line proteins in the M-line. Our morphological data indicate that the early registration of M-line proteins in primitive myofibrils may guide titin filament alignment via interaction between M-line proteins and titin. In order to investigate the role of M-line proteins in the assembly of titin filaments, anti-M-line protein or anti-titin antibodies were introduced into cultured cardiomyocytes by electroporation to functionally bind the respective proteins, and the profile of myofibril assembly was examined. Cardiomyocytes from day 2-3 cultures with incorporated anti-M-line protein antibodies became shrunk, and exhibited defective myofibrillar assembly, as shown by the failure of titin to assemble into a typical sarcomeric pattern. Incorporation of anti-titin antibody E2, which recognizes the M-line end domain of titin, resulted in the failure of M-line proteins organized into the M-line structure, as shown by random, sporadic staining with anti-M-line protein antibody. These studies confirm the essential role of M-line proteins in the organization of titin filaments in the sarcomere and that the interaction between titin and M-line proteins is crucial to the formation of the M-line structure.

The central neural mechanisms of circadian rhythm are well known in animal models but less so in humans. In this study we looked for correlations between abnormalities of circadian rhythm and the sites of stroke, with the aim of identifying the location regulating the circadian rhythm in humans. We investigated the circadian profiles of arterial pressure in 100 stroke patients by ambulatory blood pressure monitoring within 2 days after their first stroke. Patients also underwent brain computed tomography and measurements of plasma norepinephrine and adrenal hormones. A total of 52 patients (group A) had abnormal patterns of circadian blood pressure rhythm while 48 patients had normal patterns (group N). The risk of an abnormal 24-hour blood pressure pattern was strongly inversely correlated with the distance between the lesion and the hypothalamus. There was also a close positive correlation between the distance from the lesion to the hypothalamus and the circadian indices of arterial blood pressure (systolic and diastolic pressure) in both groups. Abnormal circadian changes in adrenal hormones were found in 30 of 52 patients in group A, and in nine of 48 patients in group N. Apparently, the circadian rhythm of blood pressure is modulated mainly by direct neural effects and partly by the hormonal effects of the hypothalamus and its associated neural pathways. Individualized antihypertensive treatment and additional monitoring for possible cardiac events should be performed for those at a high risk of autonomic dysfunction.

The aim of this study was to provide morphological evidence for the presence of rho A protein in developing cardiomyocytes and to investigate its possible role in myofibrillogenesis. Immunostaining with a monoclonal anti-rho antibody gave a diffuse pattern in the cytosol of cultured cardiomyocytes. Introduction of C3 exoenzyme into the cells by electroporation was used to inactivate rho A protein by ADP-ribosylation. An immunostaining with anti-vinculin, anti-talin, and anti-integrin antibodies showed the focal adhesions in electroporation control cardiomyocytes to be evenly distributed in the ventral sarcolemma; the costameric structure was also detected using these antibodies. In contrast, in C3 exoenzyme treated cells, focal adhesions were disassembled and costamere were absent; in addition, beta-actin-positive, non-striated fibrils were lost and assembly of M-protein, titin, and alpha-actinin into myofibrils was poor, as shown by diffuse and filamentous staining pattern. C3 exoenzyme treatment had a less marked effect on mature cardiomyocytes than on immature cells; in this case, cells became distorted and few myofibrils were seen. The intensity of anti-phosphotyrosine antibody staining of the focal adhesion was also decreased or diffuse in C3 exoenzyme-treated cardiomyocytes, suggesting dephosphorylation of focal adhesion components. We therefore conclude that small G protein rho A plays an important role in myofibril assembly in cardiomyocytes.

Interatrial septal dissection and penetration into the aorta by a balloon catheter occurred in a 38-year-old man with mitral stenosis as a complication of percutaneous transluminal mitral commissurotomy during trans-septal puncture. It was speculated that the thickened septum was partially punctured into the potential space between the septa primum and secundum. Then, the balloon catheter went through the interatrial septum dissection into the aortic root. Emergency surgery was performed with the catheter left in situ. The surgical findings confirmed the speculated mechanism of this rare complication. In order to avoid this complication, the location of the tip of the Brockenbrough catheter after transeptal puncture must be confirmed. Checking the left atrial pressure tracing, arterial oxygenation and contrast injection are all important and indispensable procedures.

A case-control study was carried out on 272 Chinese subjects over 40 years of age, including 157 hypertensives and 115 normotensives, to examine the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and blood pressure (BP) status. The I/D polymorphism of the ACE gene was identified by polymerase chain reaction. As a whole group, the difference of allele frequencies between normotensives and hypertensives was statistically significant (chi 2 = 4.46, P = 0.03; D/I odds = 1.46), while there was no difference in the genotype distribution (chi 2 = 3.95, P = 0.13). In a subgroup with elderly hypertension (age65), the frequencies of D-allele and DD genotype significantly increased (chi 2 = 4.43, P = 0.03 and chi 2 = 4.03, P = 0.08, respectively; D/I odds = 2.28). The association and relative risk increased further in the male gender (chi 2 = 6.65, P = 0.01 and chi 2 = 7.51, P = 0.02 respectively; D/I odds = 4.57 and DD/II odds = 12.00 respectively). The D-allele increased with age in the hypertensives, while the I-allele increased with age in normotensives. Thus, we conclude that the deletion polymorphism of the ACE gene is significantly associated with male elderly hypertension, at least in this Chinese population. This observation, if proved in a larger population, may have some implications for the prevention and treatment strategy for elderly hypertension.

One hundred fifty-six patients with rheumatic mitral valve disease were studied with transesophageal echocardiography to assess the influence of left atrial (LA) appendage size and contractile function on the occurrence of systemic embolism. LA appendage function, represented by peak emptying velocity, was found to be a better indicator than LA spontaneous echo contrast as a risk factor for systemic thromboembolism.

Conflicting viewpoints exist concerning the risk of cardiovascular morbidity for patients with white coat hypertension. The aim of this study was to compare cardiac end-organ change in white coat hypertension with persistent mildly hypertensive patients. Twenty-two white coat hypertensive patients and 15 persistently hypertensive patients were considered eligible for the study after 24 hour ambulatory blood pressure monitoring. Echocardiography was performed on all patients. The results demonstrated that both groups had similar clinical backgrounds except that white coat hypertensives were predominantly female and had less family history of hypertension. Persistent hypertensives had significantly higher average ambulatory blood pressures and pressure loads than white coat hypertensives but there was no difference in blood pressure variability. There were no differences in cardiac structural and functional changes between the two groups. As a result, we were unable to ascertain whether white coat hypertension is a benign condition. The prognostic significance of white coat hypertension requires long term follow-up and further investigation.

This study attempted to evaluate the efficacy of several "long-acting" antihypertensive agents. One-hundred consecutive hypertensive subjects with normal casual blood pressure after once-daily antihypertensive monotherapy treatment were studied. They were divided into three groups: group A, metoprolol (100 mg, daily); group B, atenolol (100 mg, daily); and group C, nadolol (80 mg, daily). Ambulatory blood pressure monitoring (ABPM) was used to evaluate the efficacy of the antihypertensive agents. The overall average ambulatory blood pressures were within the normal limits for all three groups. However, there were some abnormally high blood pressure (BP) readings shown on ABPM. Patients with an abnormally high systolic blood pressure (SBP) average140 mmHg accounted for 16.7% of group A, 19.4% of group B and 20% of group C. Those with an abnormally high diastolic blood pressure (DBP) average90 mmHg accounted for 16.7%, 19.4% and 10%, respectively, of the corresponding groups. There were no significant differences in the frequency of abnormally high SBP and DBP among the three groups. These "long-acting" antihypertensive drugs did not effectively control BP throughout the entire day. The duration of antihypertensive effect is not necessarily reflected by the blood half-life of the drug. ABPM is an effective way to ascertain the efficacy of "long-acting" hypertensive agents.

Thirty-nine patients who had rheumatic mitral valve disease in sinus rhythm were studied to compare echocardiographic and hemodynamic characteristics between those with and without left atrial (LA) spontaneous echo contrast. Patients were divided into two groups according to the presence (group 1, n = 17) or absence (group 2, n = 22) of the echo contrast. Transthoracic echocardiography and transesophageal echocardiography were performed in all patients within 1 week of cardiac catheterization study. Group 1 patients (5 men and 12 women; mean age, 47.7 +/- 13.1 years) showed smaller mitral valve area, greater transmitral valve pressure gradient, and absence of moderate to severe mitral regurgitation compared with group 2 patients (7 men and 15 women; mean age, 47.8 +/- 14.3 years). There was no significant difference in LA dimension, left ventricular end-systolic and end-diastolic dimensions, or in left ventricular ejection fraction between the two groups of patients. Left atrial appendage function was studied with Doppler in 26 patients. Patients (n = 10) with LA spontaneous echo contrast had significantly lower LA appendage ejection fraction (20.34 +/- 10.76% vs 34.16 +/- 13.13%; p0.05) and lower LA appendage peak emptying velocity (0.17 +/- 0.09 m/s vs 0.27 +/- 0.12 m/s; p0.05) than those (n = 16) without echo contrast. It is concluded that obstruction to mitral flow and altered LA appendage contractile function, not the LA size, are likely to be more important factors for the development of LA and LA appendage spontaneous echo contrast in patients with rheumatic mitral valve disease (predominant mitral stenosis) who are in sinus rhythm. These findings further substantiate that blood stasis in the LA cavity and the LA appendage is the mechanism fundamental to the formation of such spontaneous echo contrast.

To find the best predictors of outcome for patients undergoing intra-aortic balloon counterpulsation (IABP) for cardiogenic shock, we prospectively studied 30 consecutive patients by examining hemodynamic parameters and cardiac lactic acid extraction ratios before the procedure. 1 hour after and then every 6 hours for 3 days. Complete hemodynamic data were obtained from the recordings of Swan-Ganz catheterization. Blood samples were drawn from the peripheral artery, central vein, pulmonary artery wedge position (PAW) and right atrium (RA) to quantify lactic acid levels. The simplified lactic acid extraction ratio was defined as the concentration of lactic acid in RA--the concentration of lactic acid in PAW/the concentration of lactic acid in PAW. The traditional systemic lactic acid production ratio was defined as the concentration of lactic acid in the central vein--the concentration of lactic acid in the peripheral artery/the concentration of lactic acid in the peripheral artery. Of the 30 patients studied, 19 died of cardiogenic shock, (group 1), while the surviving 11 patients formed group 2. The lactic acid extraction ratios at each of the time periods after the procedure were all significantly different, while the differences in the systemic lactic acid production ratio and hemodynamic parameters, including the systemic arterial pressure, cardiac output, cardiac index and PAW pressure, became significant at varying times after IABP. In group 2, the lactic acid extraction ratios 1 hour after IABP and later were all significantly higher than at baseline. This trend was not seen in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the effects of dicentrine on the physical properties of systemic arterial trees. Dicentrine, isolated from Lindera megaphylla, was identified as a potent, selective alpha 1-adrenoceptor antagonist. We used high-fidelity multisensor catheter to measure the ascending aortic pressure and flow signals in 9 mongrel dogs. A succinct T-tube model with vascular nonuniformity was adopted to relate the pulsatile pressure and flow waves. The model-estimated parameters were capable of representing the mechanical properties of the blood vessel walls. Dicentrine had a beneficial effect on the rigidity of head and body circulation, respectively. There were great improvements not only in the tube distensibility and wave transmission time, but also in the peripheral load compliance and resistance. In global circulation that was defined as the parallel combination of head and body circulation, dicentrine significantly reduced values in characteristic impedance of the ascending aorta from 164 +/- 67 to 105 +/- 43 dynes/s/cm5, and in wave reflection factor from 0.46 +/- 0.14 to 0.36 +/- 0.13, and in total peripheral vascular resistance from 4,751 +/- 1,226 to 3,581 +/- 1,277 dynes/s/cm5. On the other hand, total peripheral load compliance was increased from 0.2950 +/- 0.1794 to 0.4457 +/- 0.2199 ml/mm Hg. Cardiac output (CO) and heart rate (HR) remained unchanged, however. Dicentrine had an impact on the mechanical properties of Windkessel vessels and resistance vessels in the systemic circulation.

The objectives of this study were to examine the serial vectorcardiographic changes following acute myocardial infarct and to assess the relationship between QRS loop changes and infarct size. Fifty adult male Long-Evans rats of 250-350 gm body weight were used to study experimental acute myocardial infarction induced by coronary artery ligation. Vectorcardiograms (VCG) of the Frank lead system were recorded before, and 1 day and 7 days after operation. Animals were sacrificed on the 7th day for histological quantitation of infarct area ratios. We found that (1) before operation, rats have ST elevation, probably due to early repolarization. (2) After coronary artery ligation, ECG showed characteristic dome-shaped ST elevation at 1 hr after ligation which returned to normal during the first day. Abnormal Q waves appeared thereafter. (3) After ligation, maximum QRS vector, ST vector and maximum T vector were reduced in magnitude the first day and recovered by the 7th day. The vectors tended to shift their direction to the right and to the posterior. QRS-T angle, however, widened as time went on. About half of the rats revealed changes in the inscription direction of the QRS loop and abnormal QRS morphology also appeared in about half of the ligated rats. (4) Those in whom abnormal QRS loop morphology and/or biting appeared had significantly larger infarct area ratios (p0.01). (5) Change in QRS loop inscription direction seemed not to be related to the infarct size. (6) In the LS plane, the difference in max QRS vector magnitude between the 1st and 7th days significantly correlated with the infarct area ratio (r = 0.533, p0.05). In the H plane, the change in the max QRS vector magnitude at the 7th day correlated with the infarct area ratio (r = -0.531, p0.05). In the F plane, changes in the direction of the max QRS vector were significantly correlated to the infarct area ratio both on the first (r = 0.431, p0.05) and 7th days (r = 0.531, p0.05). It is concluded that the VCG, like the ECG, had evolutional changes in AMI and that the QRS loop seen on vectorcardiography has only a slight correlation with the histological myocardial infarct size.

We investigated the action of two synthetic isoquinoline alkaloids, 3,4-dihydroxybenzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CSH109) and 2-bromo-3,4-dimethoxybenzyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (CSH118) on rat cardiac tissue. In the right atria, CSH109 increased the amplitude of contractions and spontaneous beats dose-dependently. In the driven left atria and right ventricular strips, CSH109 caused a similar increase in contractions. The positive inotropic and chronotropic actions of CSH109 were antagonized by propranolol. CSH118 caused the spontaneous beats in the right atria to slow down. CSH118, however, failed to antagonize the positive inotropic effect and positive chronotropic effect of isoprenaline. Electrophysiologic study revealed that 3 microM CSH118 markedly reduced fast action potential upstroke and prolonged the action potential duration (APD50) of rat ventricular cells from 34 +/- 8 msec to 122 +/- 29 msec (n = 6). CSH109 prolonged APD50 slightly from 24 +/- 4 msec to 38 +/- 7 msec (n = 4). Under voltage clamp conditions, CSH109 significantly increased the L-type calcium inward current (ICa). The TTX-sensitive sodium inward current (INa), transient outward (Ito) and late outward current (I800), however, were unaffected. The increase in ICa by CSH109 was effectively antagonized by propranolol. Contrary to the action of CSH109, CSH118 strongly suppressed INa, ICa, Ito and I400. The inhibition of INa by 1.5 to 9 microM CSH118 was associated with negative shifting of its steady state inactivation curve. It is concluded that CSH109 exerts a cardiac effect by activating the B-adrenoceptor. CSH118, however, is a broad spectrum ionic channel blocker.

EGb 761 is a preparation of Ginkgo biloba extract, which has complex biologic actions including free radical scavenging activity. To examine the anti-arrhythmic effect of EGb 761, a canine preparation of coronary artery occlusion-reperfusion was tested. Under intravenous anesthesia and open chest conditions, 32 dogs were subjected to 30 min of coronary occlusion, followed by reperfusion. Twelve received EGb 761 by intravenous injection, 1 mg/kg five minutes before coronary occlusion, followed by a continuous infusion of 0.1 mg/kg/min until five minutes after reperfusion. Immediately prior to reperfusion, an additional bolus dose of EGb 761 (1 mg/kg) was again injected (group A). The remaining 20 dogs received saline injection, and served as the control (group B). The electrocardiographic changes were recorded during the whole experimental course. The results showed that, during coronary occlusion, group A dogs had a lower count of ventricular premature beats than group B dogs. However, there was no difference in the incidence of ventricular tachycardia (VT) between the two groups. The duration of VT of the treated dogs was similar to that of the control dogs. The incidence of ventricular fibrillation (VF) was also similar. Upon reperfusion, the treated dogs were shown to be protected from VF. The duration of VT was also shorter in the treated group, although the incidence of VT was not different between the two groups. EGb 761 is effective in preventing early VF induced by coronary reperfusion while ineffective in protecting the ischemic VT and VF.

To investigate the influence of age on ambulatory blood pressure monitoring (ABPM) in hypertensive patients whose controlled casual blood pressure was normal, we studied the ABPM in 225 patients, including 122 men and 103 women, aged from 45-74 years. They were classified into three groups: Group A included 93 patients aged 45 to 54 years; Group B included 99 patients, aged 55-64 years; and Group C included 33 patients, aged 65 years and over. The various ABPM data were analyzed and compared among the three groups. The following results were found. The blood pressure (BP) averages for the whole day were normal in all three groups. There was no difference in the systolic BP average among the three groups, but the diastolic BP average declined as age increased. The variability in the systolic BP measurements increased with age. The variability in diastolic BP did not seem to change as conspicuously with age, except for the group C patients who showed a larger variability at nighttime than the other two groups. There were 123 patients (54.7%) with evidence of diurnal change in BP, and the incidence of diurnal change in BP decreased with age. The frequency of abnormally high systolic BP was similar among the three groups, but the frequency of an abnormally high diastolic BP decreased significantly with age. As for the maximal BP levels recorded in the ABPM, group C patients had a higher maximal systolic BP than the other two groups. Therefore, age has a great influence on ABPM in controlled hypertensive patients with normal casual BP.

Cardiac amyloidosis, an uncommon disease, has been reported to manifest as congestive heart failure (CHF) and/or various arrhythmias. Herein, we report a case of CHF and sick sinus syndrome. The patient, a 66-year-old man, was admitted to the National Taiwan University Hospital because of dizzy spells and recurrent syncope. Electrocardiogram showed a sinoatrial block, first degree atrioventricular block, right bundle branch block and low-voltage Q wave, R wave and S wave (QRS) complex. Prolonged corrected sinus node recovery time was documented by an atrial pacing study. A permanent pacemaker was implanted for the patient's bradyarrhythmia, but he developed progressive heart failure. Echocardiography revealed a normal-sized ventricular chamber, concentric left ventricular hypertrophy with a "granular sparkling" appearance of the myocardium, and impaired diastolic and systolic function of the left ventricle. Despite aggressive treatment, the patient expired due to intractable heart failure. Postmortem needle aspiration revealed amyloidosis involving the heart, lung and skin. We conclude that cardiac amyloidosis should be considered in elderly patients with conduction disturbance and unexplained congestive heart failure.

The presence of a valve ring abscess in patients with infective endocarditis adds appreciably to the expected rates of morbidity and mortality. From January 1989 to October 1991, a total of 43 consecutive patients with infective endocarditis seen at National Taiwan University Hospital were enrolled in this study. There were 30 men and 13 women, ranging in age from 14 to 75 years (mean +/- SD 38.5 +/- 15.0 years). The presence of infective endocarditis was documented by surgery in 26 patients and was based on a clinical diagnosis in the remaining 17 patients. A valve ring abscess was detected in five patients, either by transthoracic or transesophageal echocardiography, and all were confirmed at surgery. Aortic valve endocarditis was more frequently found in patients with valve ring abscesses (100% vs 31.6%, p0.01), and the infecting organism was most often Staphylococcus aureus (60.0% vs 15.8%, p0.05). The proportion of urgent operations was also higher in the group with abscesses (80.0% vs 23.7%, p0.05). The hospital mortality was 40.0% in patients with abscesses and 5.3% in patients without abscesses, but the difference did not reach significance (p = 0.056). Transthoracic echocardiography identified valve ring abscesses in the first three patients, but transesophageal echocardiography was more useful in detecting abscesses located in the posterior aspect of the aortic root in the other two patients, in which the lesion was overlooked or only suspected by the transthoracic approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise thallium-201 imaging using single-photon emission computed tomography (SPECT) was evaluated in 154 patients with angiographically documented coronary artery disease (CAD) and in 25 normal subjects. Of the 154 patients with CAD, 134 (87%) had abnormal thallium images. By contrast, only 77 (50%) patients had ischemic ST-segment depression (p0.001). Among 25 normal subjects, 20 had normal exercise SPECT images. The specificity of exercise SPECT imaging (80% or 20/25) in excluding patients with CAD was not significantly higher than that of exercise electrocardiography (76% or 19/25). For the detection of individual vessel involvement by analysis of territories of perfusion abnormalities, the sensitivity and specificity of exercise SPECT were 72% and 96% for the left anterior descending, 78% and 85% for the right coronary, and 47% and 98% for the left circumflex artery. Ninety (group 1) of the 154 patients with CAD achieved adequate exercise end points (ischemic ST-segment depression or85% of maximal predicted heart rate) and 64 (group 2) did not. Exercise SPECT showed significantly more perfusion abnormalities in group 1 than in group 2 (96% vs 75%, p0.001). We conclude that: (1) exercise SPECT thallium imaging is more sensitive than exercise electrocardiography for detecting patients with CAD; (2) the sensitivity of the test is affected by the level of exercise; and (3) it is valuable in the identification of individual vessel involvement.

The pathogenic role of enterovirus in patients with idiopathic dilated cardiomyopathy has been determined through a molecular biologic approach. Sensitivity in the detection of viral genomes in tissues varied between conventional nucleic acid hybridization and polymerase chain gene amplification. To improve diagnosis, we developed a strategy for reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA. We synthesized two sequence-specific oligonucleotides, primer 1 (5'dACCGACGAATACCACTGTTA3') and primer 2 (5'dCCTCCGGCCCCTGAATGCGGCTAAT3'), complementary to the 5' conserved viral genomic fragments. Viral RNA was amplified by double PCR with these two primers and hybridized with a 32-P labeled inter-primer probe (5'dATGAAACCCACAGGCACAAAG3'). Using this strategy, we detected as little as 10(-8) micrograms of coxsackievirus B3 RNA after amplification with RT-PCR, but detected none in the plasma of eight healthy adults. Among 15 patients with idiopathic dilated cardiomyopathy, viral RNA could be detected in one out of 12 plasmas (8%) and three out of four explanted heart tissues (75%). In contrast, no viral RNA could be detected in six samples of myocardial tissue from patients with other heart diseases. The only patient who had viral RNA in his plasma also had viral RNA in his myocardium. Thus, the high incidence of viral RNA in these patients suggests a possible etiologic link between them. Correct selection of specific PCR primers and the application of double PCR can improve chances of diagnosing enteroviral infection.

To study the relationship between the plasma concentration of the atrial natriuretic peptide (ANP) and heart function and to discern the secretion pathway of ANP, we determined the peripheral plasma concentration of ANP in 18 heart patients and the intracardiac concentration of ANP in six heart patients during cardiac catheterization. All plasma was extracted through a Sep-Pak C18 cartridge by acid alcohol. The concentration of ANP was determined by a sensitive and specific radioimmunoassay method. We found that the plasma ANP concentration (pg/mL) in heart patients (ranging from 12 to 139, mean = 36.1 +/- 28.9) was statistically higher than that in normal adults (ranging from 8 to 20, mean = 12.4 +/- 3.3, n = 16; p less than 0.05). The ANP level in heart patients was inversely correlated with the left ventricular ejection fraction (r = -0.53, p less than 0.05) evaluated by radionuclide angiocardiography. The intracardiac level of ANP was 88 +/- 58 at the superior vena cava, 77 +/- 55 at the inferior vena cava, 124 +/- 68 at the right atrium, 98 +/- 64 at the right ventricle, 107 +/- 58 at the pulmonary artery, 98 +/- 52 at the left ventricle, 109 +/- 73 at the aorta and greater than 351 at the coronary sinus. In conclusion, ANP is mainly secreted via the coronary sinus into the atrial cavity. The peripheral plasma ANP concentration is higher in heart patients. It increases as the left ventricular ejection fraction decreases. Therefore, plasma ANP concentration may be a useful indicator for the assessment of cardiac function.

The dipyridamole thallium-201 single photon emission computed tomography (SPECT) and resting gated blood pool ventriculography were sequentially conducted in 31 consecutive patients with angiographically proven coronary artery disease. The functional significance of various thallium redistribution patterns was assessed. The patients with an entirely complete (CR) or partial (PR) redistribution pattern had a higher global left ventricular ejection fraction than those with combined PR and no redistribution (NR), while patients with an entirely CR pattern did not have a statistically better ejection fraction than those with PR. Furthermore, myocardial segments with normal perfusion (N) and those with CR or PR had a higher regional ejection fraction than those with NR in the infero-apical area and the septal area. The regional ejection fraction was statistically higher in patients with CR than in those with PR in the septal area and higher, though not statistically significant, in the infero-apical area. The functional difference between groups with N and CR was not significant. Thus, we conclude that the redistribution patterns of dipyridamole thallium SPECT are closely correlated with systole function. Myocardium, in the presence of redistribution, will have a better functional performance in coronary artery disease.

Atrial natriuretic peptide (ANP) is a cardiac hormone with an important role in fluid, electrolyte and hemodynamic homeostasis. Rat ANP cDNA was cloned from the cDNA library constructed using 1 microgram of atrial mRNA from the heart of Wistar rats. Eight positive clones were isolated with an ANP oligonucleotide probe. One of them with about a 0.8 kb insert was selected for further subcloning and sequencing analysis. The rat ANP cDNA had 813 base pairs with a concensus sequence for transcription initiation, termination and poly A tailing. The deduced amino acid sequence contains a potential glycosylation site and two putative protease cleavage sites. Northern blot analysis showed that the ANP gene was specifically transcribed in the rat atria rather than the ventricles. The results suggest that ANP gene expression is differentially and developmentally controlled.

Disturbances in lipid metabolism have been observed during the early phase of acute myocardial ischemia. Accumulation of fatty acids in and around the ischemic cardiac cells has been implicated to play a role in both contractile and electrophysiological abnormalities. Linolenic acid is an essential fatty acid and constitutes the phospholipid moiety of the cell membrane. The purpose of this work was to study the effects of linolenic acid on the heart using canine preparations. A direct left atrial injection was used as the route of administration because intravenous injections of linolenic acid inevitably cause pulmonary edema. A surface lead electrocardiogram (ECG), an epicardial electrogram, femoral arterial pressure, left ventricular pressure and its time derivative (dp/dt) were recorded before and after drug administration. Various dosages of linolenic acid (1 mg, 5 mg, 10 mg, 20 mg, 30 mg and 60 mg/kg) and a control buffer solution were tested. The results showed that linolenic acid has a potent dose-dependent bradycardic and myocardial depression effect starting from a dose of 5 mg/kg (delta HR = -20.1 +/- 4.0 bpm, delta dp/dt = 364.3 +/- 66.0 mmHg, sec-1, p less than 0.01 vs. control). At a high dose of 30 mg/kg, linolenic acid induced premature ventricular complexes. Furthermore, ventricular tachycardia was observed in 5 of the 8 dogs (62.5%) receiving the high dose of 60 mg/kg. We conclude that linolenic acid has profound effects on the canine heart; at a low dose, it causes bradycardia and myocardial depression, while at a high dose, it also produces ventricular irritability.

Vectorcardiographic (VCG) studies were conducted in 71 patients with pure mitral stenosis (MS) documented by clinical findings, echocardiograms and cardiac catheterization. Among them, 31 were males and 40 females, with ages ranging from 20 to 58 (mean age 36.3) years. The Frank lead system was adopted for the VCG study. By VCG, 67 patients (94.4%) showed right ventricular hypertrophy (RVH), among whom 15 (21.2%) were type A, 30 (42.3%) type B and 22 (31.0%) type C. Forty-five patients (63.4%) were in sinus rhythm (NSR), while the remaining 26 (36.6%) were in atrial fibrillation (AF). Patients with type A RVH had a significantly higher pulmonary wedge (PAW) and main pulmonary arterial (MPA) pressures than those with type B or C. Patients with type C had a higher mean MPA pressure (39.0 +/- 11.3 mmHg) than those with type B (32.3 +/- 10.1 mmHg) (p less than 0.05). Among the 3 types of RVH, the mean right atrial (RA) pressures were similar (p greater than 0.05). Patients with AF had a lower mean MPA pressure, but a higher RA pressure than those with NSR (p less than 0.05). The maximal anterior force and maximal rightward force at the horizontal plane were significantly correlated with the mean MPA pressure (r = 0.54 and 0.49, respectively, both p less than 0.01), but they did not correlated well with the PAW and RA pressures (p greater than 0.05). We conclude that in patients with MS, as pulmonary hypertension progresses, VCG seems to begin with type B RVH, then emerges into type C and finally becomes type A.(ABSTRACT TRUNCATED AT 250 WORDS)

Body surface potential maps (BSPMs) and the pathology of 32 dogs with coronary artery ligations were analyzed to research the application of BSPMs to acute myocardial infarction (AMI). The group consisted of 18 dogs with left anterior descending coronary artery (LAD) ligations, 8 with right coronary artery (RCA) ligations and 6 with left circumflex coronary artery (LCX) ligations. The abnormal distribution of negative potential and minimal potential were observed in all of the dogs. In dogs with RCA ligations, the abnormal negative potential displayed on the right-superior, right-inferior or right portion of the anterior thorax. In those with LAD ligations, the abnormal potential appeared on the left-superior, left-inferior, middle-superior or middle portion of the anterior thorax. In those with LCX ligations, the abnormal potential showed on the left-superior or left-middle portion of the thorax. A good correlation was observed between the area of myocardial lesion and the extent of abnormal negative potential distribution (r = 0.82, p less than 0.001). A close correlation was also found between the area of myocardial lesion and the duration of abnormal negative potential (r = 0.61, p less than 0.05). This study suggests that BSPMs are useful in the assessment of AMI in terms of diagnosis, location and extent of myocardial infarct.

The effects of 20 microM each of amiodarone, lidocaine and quinidine on action potential and membrane currents were studied in rat ventricular cells. At a stimulation frequency of 0.1 Hz, quinidine prolonged the action potential duration (APD50) from 120 +/- 26 to 660 +/- 8 msec and increased the time to peak (Tp) amplitude from 7 +/- 1 msec to 32 +/- 6 msec. Lidocaine shortened APD50 from 123 +/- 15 to 83 +/- 6 msec without altering Tp. Amiodarone changed neither APD50 nor Tp. Voltage clamp study revealed that quinidine inhibited sodium inward current (INa) even when this current was elicited by depolarizing pulses at 0.1 Hz from a holding potential of -90 mV. For amiodarone and lidocaine, the inhibition was observed when INa was elicited from a holding potential of -70 mV. A frequency-dependent inhibition of INa by amiodarone and lidocaine was observed at frequencies higher than 1 Hz. Quinidine showed this inhibition even at 1 Hz. In correlation with the stronger frequency dependent inhibition of INa, a greater delay of the recovery and increase of the non-recovery fraction of INa was induced by quinidine. For lidocaine and amiodarone, only the recovery time constant was delayed. In cells treated with sea anemone toxin (ATX, 0.2 microM), APD50 was prolonged to 4-5 sec in 5 min. Quinidine, but not amiodarone, completely reversed the effect of ATX. Quinidine showed use-dependent inhibition of INa in these ATX-treated cells. Amiodarone, however, did not show this inhibition. It is likely that amiodarone suppresses INa by delaying the recovery of INa instead of blocking the open-state Na(+)-channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Between 1964 and 1987, a total of 57 cases of ruptured aneurysm of the sinus of Valsalva underwent surgical correction at the National Taiwan University Hospital. This represents 0.96% of all cardiac operations. The origin of ruptured aneurysm of the sinus of Valsalva was the right coronary sinus in 46, the noncoronary sinus in nine, and the left coronary sinus in two. The aneurysms ruptured into the right ventricle in 44, into the right atrium in 11, into the left ventricle in one, and into both the right ventricle and right atrium in one. Associated congenital cardiac anomalies included ventricular septal defect in 30 patients, aortic regurgitation in 20, and infundibular pulmonic stenosis and coarctation of the aorta in one each. Operative death occurred in two patients (3.5%) and one patient had a successful reoperation. The remainder did well following surgery. To compare the differences between Oriental and Western countries in ruptured aneurysm of the sinus of Valsalva, 361 cases (195 Oriental patients versus 166 Western) were collected from the literature. Analyses of these cases revealed that ruptured aneurysm of the sinus of Valsalva in Oriental patients compared with Western series is characterized by a higher incidence (5 times), more aneurysms originating from the right coronary sinus (87.9% versus 63.6%), more aneurysm rupturing into the right ventricle (84.2% versus 56.6%), a higher incidence of association with ventricular septal defect (mainly supracristal) (59.0% versus 34.6%), less incidence of association with other congenital cardiac abnormalities (4.1% versus 21.5%), very few instances of rupturing into cardiac chambers other than the right ventricle and right atrium, and less incidence of occurrence in the extremities of ages (the youngest was 7 years in Oriental patients versus 11 months in the Western series). In other words, ruptured aneurysm of the sinus of Valsalva in Oriental patients is more or less a simple and uniform disease entity in contrast to the more diverse and protean pathologic profiles encountered in Western series. However, both Oriental patient and Western patient series have similar incidences of combination with aortic regurgitation (24.6% versus 20.0%), with 40.4% of Oriental patients and 60.6% of Western patients presenting with intact ventricular septum. Therefore the pathogenetic mechanisms of ruptured aneurysm of the sinus of Valsalva may at the same time contribute to the development of aortic regurgitation.

Noninvasive ambulatory blood pressure monitoring (NABPM) has been playing an increasing role in the diagnosis of hypertension and in the evaluation of antihypertensive drugs. NABPM data for the normal Chinese population has not yet been established. However, data obtained from 25 young male Chinese adults has been analysed. Average ambulatory blood pressure was 120 +/- 8/74 +/- 7 mmHg for the whole-day monitoring. There was an evident diurnal change of blood pressure during the 24-hour monitoring period with higher blood pressure levels being recorded during the daytime, rather than during the nighttime (7.8 +/- 9.7/4.4 +/- 4.8 mmHg; p less than 0.001). Maximal hourly blood pressure averages occurred during the late morning, while minimal hourly blood pressure averages occurred around midnight. The variability in blood pressure was 11 +/- 3/9 +/- 2 mmHg for the daytime and 11 +/- 3/8 +/- 2 mmHg for the nighttime. The incidence of abnormally high blood pressure ranged widely. Eating would raise both the systolic and diastolic blood pressure, while sleep caused a significant fall in blood pressure. This study offers basic data for the study of NABPM in young normotensive Chinese adults.