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Biomedical subjects

S H Sheu

Publications and source records attributed to S H Sheu.

At least 19 recordsLinked to original sources

Effects of verapamil, propranolol, and procainamide on adenosine-induced negative dromotropism in human beings.

Adenosine, verapamil, propranolol, and procainamide are widely used antiarrhythmic drugs. The interactions among them are still not known in human beings. Adenosine-induced negative dromotropic effects were assessed by rapid bolus injection of adenosine during constant high right atrial pacing in each patient. The initial dose of adenosine was 0.5 mg and was followed by a stepwise increment of 0.5 mg until atrioventricular (AV) nodal block occurred. The negative dromotropic actions of adenosine were examined in the control state and in the following three protocols in three groups of patients: (1) In 12 patients (group 1), intravenous verapamil, 0.15 mg/kg, was given; (2) In 12 patients (group 2), intravenous propranolol, 0.1 mg/kg, was given; and (3) in 10 patients (group 3), intravenous procainamide, 15 mg/kg, was given. The dose-response curves of adenosine on AV nodal conduction were almost identical in the control state and after verapamil, propranolol, or procainamide injection. However, verapamil, in contrast to propranolol, significantly reduced the dose of adenosine required to produce AV nodal block, from 4.4 +/- 0.7 mg to 2.7 +/- 0.3 mg (p < 0.01). Of note, procainamide exerted no significant effects on adenosine-induced negative dromotropism on AV nodal conduction or AV nodal block. In conclusion, the negative dromotropic effects of adenosine are preserved and independent even in the presence of verapamil, propranolol, or procainamide. Both verapamil and propranolol can exhibit additive effects with adenosine in prolonging AV nodal conduction time; however, only verapamil can reduce the dose of adenosine required to produce AV nodal block. This finding indicates that the dose of adenosine may be reduced for patients who have already been treated with verapamil.

Adenosine

Capsinolol: the first beta-adrenoceptor blocker with an associated calcitonin gene-related peptide releasing activity in the heart.

1. The beta-adrenoceptor blocking and calcitonin gene-related peptide (CGRP)-releasing properties of capsinolol (N-[4-(2-hydroxy-3 (isopropylamino) propoxy)-3-methoxybenzyl]-nonanamide), derived from nonivamide, were investigated under in vivo and in vitro conditions. 2. Capsinolol (0.1, 0.5, 1.0 mg kg-1, i.v.), as well as (+/-)-propranolol, produced a dose-dependent bradycardia response and a temporary pressor action in urethane-anaesthetized normotensive Wistar rats. These cardiovascular effects were different from the vagus reflex and parasympathetic efferent effects shown by capsaicin (0.1 mg kg-1, i.v.) in the rat. 3. Capsinolol (1.0 mg kg-1) inhibited the tachycardia effects induced by (-)-isoprenaline, but had no blocking effect on the arterial pressor responses induced by (-)-phenylephrine. The findings suggest that capsinolol possesses beta-adrenoceptor blocking activity, but it has no alpha-adrenoceptor blocking activity. 4. In guinea-pig isolated tissues, capsinolol (10(-8) to 10(-6) M) antagonized (-)-isoprenaline-induced positive chronotropic and inotropic effects of the atria and tracheal relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)-isoprenaline suggests capsinolol is a beta-adrenoceptor competitive antagonist. 5. Capsinolol (10(-5) to 10(-4) M) exhibited a positive cardiotonic effect that was not inhibited by (+/-)-propranolol and reserpine, but was inhibited by capsazepine (10(-6) M) and CGRP8-37 (10(-6) M). This effect was independent of intrinsic sympathomimetic effects. 6. An immunoassay of released CGRP from guinea-pig isolated perfused heart indicated that capsinolol increases the release of CGRP and thus produces positive cardiotonic effects. 7. In conclusion, capsinolol is a non-selective beta-adrenoceptor antagonist with capsaicin-like cardiotonic properties unrelated to traditional intrinsic sympathomimetic effects. It is suggested that capsinolol causes CGRP release from cardiac sensory neurones via a non-adrenergic mechanism and then activates CGRP receptors on cardiac muscle.

Adrenergic beta-1 Receptor Antagonists

Electrophysiological manifestations of the excitable gap of slow-fast AV nodal reentrant tachycardia demonstrated by single extrastimulation.

BACKGROUND: Although AV nodal reentrant tachycardia (AVNRT) is a well-known rhythm disorder, its anatomic substrate and electrophysiological mechanism remain to be defined. Previously, the description of the excitable gap (EG) of AVNRT was based on electrical stimulation performed from sites remote from the reentrant circuit. In the present study, we characterized the EG of AVNRT by atrial extrastimulation close to the putative reentrant circuit in the AV junction. METHODS AND RESULTS: In 16 patients (3 men, 13 women; mean age, 45 +/- 13 years) with inducible slow-fast AVNRT (mean cycle length, 353 +/- 52 ms), single extrastimuli with a 10-ms decrement in the premature coupling interval were delivered from the anterosuperior interatrial septum (fast pathway area) and the posteroinferior interatrial septum (slow pathway area) from late diastole until atrial refractoriness. An EG was considered present when resetting or termination of AVNRT was induced by single atrial extrastimulation. The study showed that the duration of the EG of AVNRT was wide, measuring 121 +/- 56 and 123 +/- 47 ms and occupying 33 +/- 11% and 34 +/- 9% of the tachycardia cycle length during single extrastimulation from the slow pathway area and the fast pathway area, respectively. The resetting pattern most commonly manifested as the sum of the coupling interval and the return cycle being less than a fully compensatory pause (two times the basic tachycardia cycle length). However, patterns equal to and greater than a fully compensatory pause were also observed. Of note, in 2 of the 16 patients, atrial extrastimulation from either the fast or slow pathway area also affected the preceding tachycardia cycle length (HH interval), indicating alteration of the anterograde input. In all patients, the curve derived from plotting the coupling interval of extrastimuli against the return cycle during resetting exhibited an "increasing" pattern. The mode of tachycardia termination usually occurred when the premature atrial impulse was orthodromically blocked in the anterograde slow pathway. CONCLUSIONS: The EG of slow-fast AVNRT is relatively wide, as demonstrated by single atrial extrastimulation from the interatrial septum near the AV junction. Overall, the electrophysiological manifestations of the EG of AVNRT are very similar to those described in AV reciprocating tachycardia incorporating an accessory connection. These findings lend further support to the notion that, in humans, AVNRT involves a reentrant mechanism with a wide excitable gap.

Adolescent

Effects of contrast media on coronary hemodynamics and myocardial metabolism.

RATIONALE AND OBJECTIVES: This study was designed to compare the effects of ionic contrast medium (CM), Renografin-76 (R76), and nonionic CM, Omnipaque-350 (OM350), on coronary hemodynamics and myocardial metabolism. METHODS: In 10 open-chest, atrial-paced dogs, 4 mL of R76 and OM350 were injected into the left anterior descending coronary artery. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), lactate extraction (LE), left ventricular (LV) dp/dt, and aortic systolic pressure (AOP) were measured. RESULTS: The maximal CBF changes caused by OM350 and R76 were 23.7 +/- 3.3 mL/minute and 18.3 +/- 3.3 mL/minute (NS), respectively. OM350 produced an increase in LV dp/dt by 378 +/- 85 mm Hg/second, which was different from -244 +/- 65 mm Hg/second by R76 (P < .05). The changes in MVO2 and LE after OM350 injection were 2.6 +/- 0.6 mL/minute and 10.2 +/- 5 microM/minute, respectively; those were different from -0.1 +/- 0.4 mL/minute, and -7.7 +/- 5.1 microM/minute after R76 injection (P < .05). CONCLUSION: Although both agents increased CBF, they appeared to act by different mechanisms. That a direct coronary vasodilator effect is the main action of R76 on coronary vascular response is suggested by decreasing myocardial contractility and oxygen consumption. However, OM350, by enhancing both parameters, may augment CBF at least in part by autoregulation.

Animals

Sick sinus syndrome with normal atropine response--a case report.

A 76-year-old woman was admitted due to recurrent syncope. Sinus bradycardia and intermittent sinus pauses (up to 2.24 sec) were documented by 24 hour Holter electrocardiogram. Although intravenous atropine can increase the sinus rate up to 100 bpm, electrophysiologic study showed marked prolongation of sinus node recovery time both at the control state and after autonomic blockades. Sick sinus syndrome was diagnosed, even with a normal atropine test, and a permanent pacemaker resulted in resolution of the syncope.

Aged

The circadian variations of blood pressure and heart rate in patients with mitral valve prolapse.

It is well known that both normal subjects and hypertensives manifest a distinct nocturnal fall of arterial blood pressure and heart rate. But till now there has been no report about the diurnal change of blood pressure and heart rate in MVP patients. In this report we studied the circadian variations of blood pressure and heart rate in 18 symptomatic MVP patients (mean age 32 +/- 10 years) and compared them with those in 18 age- and sex-matched normal control subjects (mean age 35 +/- 9 years). The MVP group presented a statistically significant blunting of the nocturnal fall in systolic blood pressure (4.2 +/- 3.6% vs 9.7 +/- 3.7%, p = 0.0002). No obvious difference in the nocturnal fall in heart rate was noted between both groups (20.2 +/- 6.0% vs 18.8 +/- 5.6%, p = 0.4290). In conclusion, the circadian variation of blood pressure was blunted in patients with mitral valve prolapse. The mechanism is uncertain and further studies are necessary to clarify it.

Adult

Comparison of the electrophysiologic effects of oral sustained-release and intravenous verapamil in patients with paroxysmal supraventricular tachycardia.

The electrophysiologic effects of intravenous verapamil (0.15 mg/kg) and oral sustained-release verapamil (verapamil-SR) (240 mg once daily for 7 days) were studied in 17 patients with paroxysmal supraventricular tachycardia (SVT). Ten patients had atrioventricular (AV) nodal reentrant tachycardia and 7 had AV reciprocating tachycardia involving an accessory AV pathway. Both preparations significantly prolonged anterograde effective refractory period of the AV node and depressed the retrograde AV nodal conduction system. The sinus cycle length, and atrial and ventricular effective refractory periods were prolonged after oral verapamil-SR. Furthermore, oral verapamil-SR depressed retrograde accessory pathway conduction which was not interfered with by intravenous verapamil. Intravenous verapamil and oral verapamil-SR prevented induction of sustained SVT in 12 of 17 (71%) and 10 of 17 (59%) patients, respectively. Follow-up study with oral verapamil-SR 240 mg once daily in 15 patients for 19 +/- 6 months revealed that among the 8 patients without induction of sustained SVT, 7 have been free of symptomatic arrhythmia; only 1 patient had occasional SVT attacks. For the 7 patients with induction of sustained SVT, 3 patients failed to respond to oral verapamil-SR, 1 patient became symptom free, and the remaining 3 patients had less frequent SVT attacks. Thus, immediate intravenous verapamil testing predicts the electrophysiologic results of oral verapamil-SR therapy, and oral verapamil-SR once daily may be used for long-term prophylaxis of SVT with better patient compliance.

Administration, Oral

Comparison of hepatitis C virus strains obtained from hemodialysis patients.

To understand what genotypes of hepatitis C virus (HCV) exist in Taiwan, we chose the non-structure 5 (NS5) region of the HCV genome for the target area of reverse transcription-polymerase chain reaction (RT-PCR) to detect HCV RNA from sera of hemodialysis patients. Of 39 serum samples which were positive for the HCV antibody among 87 samples from hemodialysis patients, 12 (antibody against HCV core protein, OD > 2) were examined by the RT-PCR. The plasmid pUC19 was used to clone HCV cDNAs in the NS5 region (401 bp) derived from 11 serum samples which were positive for HCV RNA. Sequence analyses of individual clone of these 11 amplified cDNA fragments were performed. Dr. Cha's classification (16) suggested that two genotypes of HCV were found in these serum samples; type II (2/18.2%) and type III (9/81.8%). Our study indicates also that NS5 is an adequate target region to differentiate HCV strains derived from different patients in the same hospital. The analysis of the amplified cDNA in the NS5 region of the HCV genome will therefore provide suitable information to perform a molecular epidemiological study on the transmission routes of this important virus infection.

Amino Acid Sequence

Sequence analysis of nucleocapsid and partial envelope genes of the hepatitis C virus derived from an aboriginal asymptomatic carrier.

Two overlapping cDNA fragments of the 5'-terminal region of the hepatitis C virus (named as HCV-B) were cloned by reverse transcription-polymerase chain reaction (RT-PCR). The consensus nucleotide sequence of the 1101 nucleotide length was constructed from the sequences of at least three independent clones of each one of these two amplified overlapping HCV cDNA fragments. By comparison with other HCV strains isolated from different countries, the 5' non-coding region was almost identical, with only 1 difference in 90 nucleotides, and the homology of the putative nucleocapsid gene was found to be quite conservative, with a similarity of 90-96% and 96-97% at the nucleotide and amino acid levels, respectively. The homology of the down-stream region which encodes a putative envelope protein showed a low degree of identities (71.5% and 76.7% compared with American HCV-1 strain) at the levels of nucleotide and amino acid. On the other hand, it was similar to the Taiwanese HCV-T strain and the Japanese major J1 strain; the homology was about 93% at both levels of nucleotide and amino acid. This finding led to a conclusion that the HCV-B strain is closely related to the major HCV genotypes as HCV-J1 and HCV-T, isolated in Asian area.

Amino Acid Sequence

Cardiac amyloidosis--a case report.

A 52-year-old male patient presented with resistant congestive heart failure. Echocardiographic findings revealed increased right ventricular (RV) wall thickness in conjunction with concentric left ventricular (LV) hypertrophy, LV systolic dysfunction and a granular sparking myocardial appearance. Doppler assessment showed a restrictive LV and RV diastolic filling pattern. These echocardiographic features combined with low voltage of the electrocardiogram is highly suggestive of cardiac amyloidosis. The diagnosis was confirmed by cardiac catheterization and endomyocardial biopsy.

Amyloidosis

Effect of ionic contrast medium on plasma atrial natriuretic peptide.

To evaluate the effect of ionic contrast medium on plasma atrial natriuretic peptide (ANP) and its contributing factors, we measured plasma ANP, serum osmolality, pulmonary capillary wedge pressure (PCWP), femoral artery systolic pressure (FASP), and heart rate before and after left ventriculography with Rayvist in 13 patients suspected of coronary artery disease. The control values of plasma ANP, serum osmolality, and PCWP were 20.3 +/- 5.1 pg/ml, 293.5 +/- 1.5 mosm/kg, 6.6 +/- 0.8 mm Hg, respectively. Rayvist produced a significant increase in plasma ANP, serum osmolality, and PCWP at 1 minute (26.0 +/- 6.3 pg/ml, p < 0.05; 300.7 +/- 1.9 mosm/Kg, p < 0.001; 10.7 +/- 1.3 mm Hg, p < 0.001) and 5 minutes (27.3 +/- 6.3 pg/ml, p < 0.01; 296.8 +/- 1.9 mosm/Kg, p < 0.001; 10.4 +/- 1.7 mm Hg, p < 0.01) post left ventriculography. The FASP decreased significantly at 1 minute, followed by an insignificant increase at 5 minutes. The heart rate increased significantly at 1 minute but no significant change was noted at 5 minutes. We conclude that plasma ANP increases significantly after left ventriculography with Rayvist and its response may be related to left ventricular filling pressure and serum osmolality, but not to FASP or heart rate.

Adult

Effects of intracoronary administration of contrast media on myocardial high-energy phosphate. A comparison of sodium meglumine diatrizoate and iohexol.

Myocardial ATP, ADP, and AMP were measured from cardiac biopsy in 11 dogs after intracoronary injection of 6 mL of sodium-meglumine diatrizoate (SMD), iohexol (IOH), or 0.9% sodium chloride (NaCl), and in three of the dogs at baseline before any injection. The ATP at baseline and after SMD, IOH, and 0.9% NaCl were 5.39 +/- 0.41, 3.72 +/- 0.70, 5.52 +/- 0.82, and 5.44 +/- 1.40 mumol/g wet weight, respectively. There were significant differences between SMD and IOH (P less than .02), and between SMD and 0.9% NaCl (P less than .05). The energy charge of SMD was 0.82 +/- 0.08, which differed from 0.89 +/- 0.02 for NaCl or 0.9 +/- 0.05 for baseline (P less than .05), but not from 0.85 +/- 0.04 for IOH. In conclusion, diatrizoate caused significant depletions in ATP stores in comparison with iohexol, but there was no significant difference with respect to energy charge. Nonionic contrast media would be preferable for coronary arteriography in patients whose high-energy stores might be depleted from severe ischemia.

Adenosine Diphosphate

Effects of intracoronary administration of contrast media on coronary hemodynamics in a canine post ischemic reperfusion model.

Hemodynamic changes due to intracoronary injections of nonionic contrast medium Omnipaque-350 (OM), ionic dimer Hexabrix (HB), and ionic contrast medium Renografin-76 (R76) were compared at baseline and during reperfusion after a 30-minute left anterior descending coronary artery (LAD) occlusion. In 11 open chest, anesthetized, and atrially paced dogs, 4 ml of either OM, HB, R76, or 0.9% NaCl were injected into the carotid-LAD bypass system. Coronary blood flow (CBF) and coronary vascular resistance (CVR) were measured before, during and after the intracoronary injection. The maximal hyperemic change (in percentage) from the preinjection value of CBF and CVR were calculated. The results at baseline and during reperfusion for CBF were: 104 +/- 14% vs. 85 +/- 10% for OM (NS); 76 +/- 11% vs. 39 +/- 9% for R76 (p less than 0.05); 57 +/- 8% vs. 33 +/- 5% for HB (P less than 0.05); and 30 +/- 7% vs. 9 +/- 4% for 0.9% NaCl (p less than 0.05). Consequently, the hyperemic changes of CVR at baseline and during reperfusion were: -49 +/- 3 vs. -42 +/- 4% for OM (NS); -44 +/- 3% vs. -24 +/- 6% for R76 (p less than 0.01); -36 +/- 3% vs. -24 +/- 4% for HB (p less than 0.05); and -18 +/- 4% vs. -7 +/- 3% for 0.9% NaCl (p less than 0.05). Thus, ischemia and reperfusion significantly dampened the coronary hemodynamic and vascular response to R76, HB, and 0.9% NaCl but not to OM. The preserved coronary vascular reserve with high flow in this canine post-ischemic reperfusion model may explain the advantage of nonionic over ionic contrast media used in emergency coronary angiography following thrombolysis.

Animals

Is sick sinus syndrome an adenosine-mediated disease? Effects of intravenous aminophylline on sick sinus node function after pharmacologic autonomic blockade.

To assess the effects of intravenous aminophylline on the sinus node, 12 patients with clinical and Holter monitor-documented sick sinus syndrome were studied (1) during the control state, (2) after pharmacologic autonomic blockade and (3) 5 min after intravenous administration of aminophylline. The effects of aminophylline on sinus node function were compared with those after pharmacologic autonomic blockade. No significant improvement of sinus node function was found after intravenous aminophylline administration with a mean sinus cycle length and a mean maximum CSRT of 968 +/- 218 and 1832 +/- 1036 ms, respectively. The mean serum theophylline level was 10.9 +/- 1.7 micrograms/ml. Since aminophylline is an adenosine receptor antagonist, these findings suggest that intrinsic adenosine may not play an important role in pathogenesis in patients with chronic and advanced sick sinus syndrome.

Adenosine

Molecular cloning of cDNA of hepatitis C virus (HCV) genome from a healthy carrier in an aboriginal community in Taiwan with high prevalence of HCV infection.

We analyzed hepatitis C virus (HCV) obtained from a healthy HCV carrier in an aboriginal community with high prevalence of HCV infection. By use of random primers and specific oligonucleotide primers, a cDNA fragment of putative non-structural 3 (NS3) region of the HCV genome was cloned by reverse transcription-polymerase chain reaction (RT-PCR) using RNA extracted from a serum sample of a healthy HCV carrier in Taur-Yuan village. The nucleotide and deduced amino acid sequences from the 583 nucleotides long cDNA were compared with those of equivalent region of HCV of other previously reported clones: [J1, HCV-J (regarded as major type of HCV in Japan) and US prototype]. They had 93.7% (546/583), 93.1% (543/583) and 80.4% (469/583) homology at the nucleotide level and 96.9% (188/194), 96.9% (188/194) and 91.8% (178/194) homology at the amino acid level, respectively. These results showed that HCV prevalent in an aboriginal community in Taiwan is more similar to Japanese type than to the US prototype.

Amino Acid Sequence

Effect of heparin in nonionic contrast media on blood coagulation and its dose response curve.

To investigate the local effect of heparin on blood clot formation and partial thromboplastin time (PTT), blood was withdrawn into the catheters filled with iopamidol and heparin at 0, 1, 2, 3, 5, and 10 U per ml concentrations as debubbling. After 30 min incubation, blood clotting was observed in all 8 experiments with heparin concentrations of 0 and 1 U per ml; in 3 of 8 with 2 U per ml; and in none with greater than or equal to 3 U per ml. PTT of blood and contrast mixture in catheters increased significantly when heparin concentrations were increased from 2 to 3 U per ml and reached a level of greater than 110 sec at 5 or more U per ml. Thus, the addition of heparin to nonionic contrast media at concentrations of 5 U per ml may be an easy measure with which to prevent blood clotting and reduce thromboembolic complications during coronary arteriography.

Blood Coagulation

The effect of sodium on hemodynamic changes during coronary angiography with nonionic contrast media.

To investigate the effect of sodium on cardiac hemodynamics, sodium chloride was added to nonionic contrast media to a 0.9% concentration and was compared with the standard media iohexol, iopamidol, and ioversol. Left coronary angiography was performed in 10 closed-chest, atrial-paced dogs with 10 ml injections of each preparation in a randomized and blinded fashion. The maximum changes in left ventricular systolic pressure, mean aortic pressure, left ventricular and diastolic pressure, and maximal rise of left ventricular pressure were measured. The left ventricular systolic pressure and mean aortic pressure decreased by 17 +/- 7 mm Hg and by 12 +/- 5 mm Hg with iohexol plus 0.9% NaCl, but only by 5 +/- 4 mm Hg and by 4 +/- 3 mm Hg with iohexol alone (p less than 0.001). The left ventricular and end diastolic pressure increased by 2.2 +/- 0.6 mm Hg with iohexol plus 0.9% NaCl, but did not change with iohexol alone (p less than 0.001). Left ventricular dp/dt decreased by 204 +/- 161 mm Hg/sec with iohexol plus 0.9% NaCl but increased by 392 +/- 122 mm Hg/sec with iohexol alone (p less than 0.001). Similar results were obtained from experiments with iopamidol versus iopamidol plus 0.9% NaCl and ioversol versus ioversol plus 0.9% NaCl. Ioversol plus 5% dextrose or ioversol plus 2.1% choline chloride (isomolar to ioversol plus 0.9% NaCl) produced a significant increase in left ventricular systolic pressure and left ventricular dp/dt (versus ioversol plus 0.9% NaCl, p less than 0.001). Thus, sodium, but not the osmolality or chloride, contributed to the negative inotropic effect of the contrast media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals