Atrial fibrillation and continuous hypotension induced by sildenafil in an intermittent WPW syndrome patient.

A 55-year-old Japanese man was hospitalized for palpitations and severe chest oppression one hour after he ingested about 1500 ml of beer and sildenafil (Viagra) 50 mg. At 43 years of age, he had been diagnosed with intermittent WPW syndrome following a paroxysmal supraventricular tachycardia (PSVT) attack. He took a 1 mg tablet of doxazosin daily for mild hypertension. On admission, his blood pressure was 90/54 mmHg and his heart beat was weak and irregular with a rate of about 220/min. Since atrial fibrillation (Af) was diagnosed on an electrocardiogram (minimum RR interval; 0.22 seconds), direct current shock was performed with 100 joules and 150 joules but conversion to sinus rhythm failed. Sinus rhythm returned spontaneously from Af four hours after taking sildenafil. Since blood pressure was 50/17 mmHg despite the return to sinus rhythm, blood pressure was maintained by dopamine for twelve hours after sinus rhythm returned. The patient underwent catheter ablation for curative therapy and thereafter has not had any further episodes of tachycardia.

Right ventricular dysplasia with complete atrioventricular block: necessity and limitation of left ventricular epicardial pacing.

This paper reports a case of right ventricular dysplasia, in which the patient presented with atrioventricular block and was followed for more than 8 years under left ventricular epicardial pacing. Five years after first epicardial pacemaker implantation, loss of capture occurred. Replacement of the epicardial leads was performed.

Effect of mitral valvuloplasty in mitral stenosis on coagulation activity.

We investigated the plasma levels of molecular markers for the status of thrombin generation and fibrinolysis in patients with mitral stenosis before and after percutaneous mitral valvuloplasty. Our results show that percutaneous mitral valvuloplasty results in decreased coagulation activity, suggesting that percutaneous mitral valvuloplasty is also useful for prevention of systemic embolism in patients with mitral stenosis.

Expression of cytokine-induced neutrophil chemoattractant in rat cardiac myocytes.

Accumulation and adhesion of leukocytes to cardiac myocytes play important roles in the pathogenesis of inflammation-mediated myocardial injury such as ischaemia/reperfusion and myocarditis. The involvement of leukocyte chemotactic factors has been speculated in these processes. We investigated the expression of cytokine-induced neutrophil chemoattractant (CINC) in rat cardiac myocytes. CINC is a rat equivalent of human interleukin-8. On exposure to interleukin-1 alpha (IL-1 alpha), cultured neonatal rat cardiac myocytes released appreciable levels of CINC both dose- and time-dependently. Tumor necrosis factor-alpha and lipopolysaccharide also significantly increased CINC accumulation in the culture supernatant. CINC mRNA expression was not observed in unstimulated myocytes, however, the expression was markedly induced by exposure to IL-1 alpha with a peak elevation at 3 h. Potent chemotactic activity for neutrophils was detected in the supernatant of cultured rat cardiac myocytes by stimulation with IL-1 alpha. This IL-1 alpha-induced chemotactic activity was significantly inhibited by polyclonal anti-CINC antiserum. Addition of dexamethasone, genistein, actinomycin D or cycloheximide significantly suppressed the IL-1 alpha-induced CINC accumulation. Under hypoxia (95%N2 + 5%CO2), CINC accumulation was increased in a time-dependent manner, and reoxygenation after hypoxia further intensified CINC accumulation. This hypoxia reoxygenation-induced CINC expression was significantly inhibited by pretreatment with dexamethasone. In conclusion, inflammatory stimuli induce the expression of CINC in rat cardiac myocytes, which may lead to myocardial injury via accumulation and activation of neutrophils.

A phospholipase A2 inhibitor (Ro 31-4493) prevents protein loss associated with the calcium paradox in isolated guinea pig hearts without effect on contracture, calcium overload, or the currents through L-type calcium channels.

OBJECTIVE: Although it is widely accepted that the hypercontraction provoked by the influx of Ca2+ on return to normal Tyrode solution after a period of Ca2+ depletion (the calcium paradox) contributes to the damage to the cell membrane, it remains possible that the Ca2+ overload activates intracellular enzymes that are important in the initial degradation of the cell membrane. This possibility was examined in this work. EXPERIMENTAL DESIGN: The effect of Ro 31-4493, a phospholipase A2 inhibitor, upon protein loss, hypercontracture, and ultrastructural changes in Langendorff perfused guinea pig hearts during the calcium paradox was studied. Because the degree of Ca2+ overload might also be affected, the action of the drug on the resting and action potentials and the whole cell currents through the L-type Ca2+ channels and the changes in [Ca2+]i in isolated guinea pig ventricular myocytes were also studied. RESULTS: Ro 31-4493, at 10-50 microM, inhibited the release of proteins from guinea pig Langendorff perfused hearts during the calcium paradox in a dose dependent way. This protective effect required preincubation with the agent before the Ca2+ depletion. No significant effect upon the contractile behaviour, as recognised from the sustained increase in intraventricular pressure on Ca2+ repletion, was produced. However, structural changes suggest that the extent of hypercontraction, the disruption of cell membrane and the release of mitochondria was less in treated hearts. Ro 31-4493 produced no change in the resting and action potentials or the behaviour of the L-type Ca2+ channels with either Ca2+ or Na+ as the charge carrier, while measurements of [Ca2+]i indicated a similar Ca2+ overload in both treated and untreated hearts. CONCLUSION: The effects of Ro 31-4493 are inconsistent with mechanical consequences of hypercontraction upon activation of a Ca2+ dependent phospholipases may be an important step.

Changes in mitochondrial function induced in isolated guinea-pig ventricular myocytes by calcium overload.

1. Changes in [Ca2+]i and pHi, mitochondrial membrane potential (psi m) and mitochondrial [NADH] have been measured independently using fluorescent techniques in single isolated guinea-pig ventricular myocytes subjected to Ca2+ overload. 2. The changes in NADH autofluorescence on the inhibition or uncoupling of respiration are consistent with the signal emanating from the mitochondrial NADH. 3. Removal of Ca2+ and Mg2+ from the bathing Tyrode solution induced a modest fall in both [Ca2+]i and pHi, a small slowly developing depolarization of psi m and an initial fall followed by a rise in mitochondrial [NADH]. 4. In myocytes that maintained an intact sarcolemma, return to Ca(2+)-containing fluid elicited a strong but brief intracellular acidification, a rise in [Ca2+]i which generally recovered more slowly to stabilize above the initial level in Tyrode solution, a steep fall in mitochondrial [NADH] and a brief transient recovery followed by a large sustained depolarization of psi m. NADH autofluorescence and mitochondrial depolarization often reached values that were not further increased by uncoupling respiration although recovery of NADH was elicited by inhibitors of respiration. 5. These changes were reduced when the Ca2+ overload was less severe as evidenced by a reduced hypercontracture upon Ca2+ repletion. A similar reduction could be routinely achieved by elevation of [Mg2+]o during the period of Ca2+ depletion. 6. These results suggest that the well-established depletion of energy-rich phosphates that occurs on Ca2+ overload is due to the combined effects of the failure of the citric acid cycle to provide sufficient mitochondrial NADH for the respiratory chain and an uncoupling of respiration from ATP production due to depolarization of psi m. The former effect could result from the depletion of sarcoplasmic amino acids and the latter from increased Ca2+ cycling across the mitochondrial wall provoked by the elevated [Na+]i and [Ca2+]i.

The role of the sodium pump and sodium-calcium exchange in recovery from calcium overload in guinea-pig ventricular myocytes.

A marked increase in [Ca2+]i is provoked in isolated guinea-pig ventricular myocytes by return to normal Tyrode solution after a period of exposure to fluid free of divalent cations. When the sarcolemma of the myocyte remains intact, [Ca2+]i falls back towards initial levels over the next 5 to 10 min in spite of the strong irreversible contracture. This recovery fails to occur if either the Na+ pump or Na(+)-Ca2+ exchange is inhibited once [Ca2+]i has risen.

The failure of radical scavengers to attenuate the incidence of reperfusion arrhythmias despite improvement of cardiac function.

We studied the concomitant effects of scavengers of reactive oxygen species (ROS) on both cardiac function and the incidence of arrhythmias. Isolated rat heart was perfused with a working mode paced at 300 beats/min. The left coronary artery was occluded for 5, 7, 15, or 60 min and reperfused thereafter for 30 min. Superoxide dismutase and catalase were infused from 5 min prior to reperfusion to the end of reperfusion in the scavenger treatment group. In the 60-min ischemia group with scavenger treatment, the cardiac output was significantly higher than that in the untreated group at both 10 and 30 min of reperfusion (P less than 0.01). In the 15-min ischemia group with scavenger treatment, the cardiac output showed a tendency toward a higher value than that in the untreated group. The incidence of reperfusion arrhythmias occurring after a short ischemic time (5, 7, or 15 min) were similar in the scavenger treated and untreated groups; but, with a preceding ischemia of 60 min, the incidence of ventricular tachycardia was higher in the scavenger treated group than in the untreated group (P less than 0.02). In conclusion, scavengers improved contractile dysfunction but did not attenuate the incidence of arrhythmias.

The demonstration of DMPO superoxide adduct upon reperfusion using a low non-toxic concentration.

Experiments were conducted in an attempt to circumvent the problem associated with the use of a high concentration of the spin trap, 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), which has been suggested to have serious toxic effects on tissue. A low concentration of DMPO (10 mM) was used to detect the free radical generation in hearts with ischemia/reperfusion insult. In the effluent immediately after reperfusion, DMPO-OOH, a superoxide spin adduct of DMPO, was obtained. DMPO in that concentration range did not interfere at all with the left ventricular (LV) function during the control perfusion period. Even after reperfusion, LV function was not depressed any more than that occurring in hearts without DMPO, whereas DMPO of the conventional concentration (100 mM) markedly depressed the ventricular function. Enzyme leakage from hearts also supported non-toxicity finding of DMPO at 10 mM; confirming that the DMPO superoxide adduct is real evidence of the generation of superoxide upon reperfusion and is not attributed to an artificial generation due to the cytotoxicity of DMPO.

The detection of technical failures in perfused heart with ischemia and reperfusion by epicardial NADH fluorescence.

This study documents the value of continuous observation of nicotinamide adenine dinucleotide (NADH) fluorescence (NADH-F). NADH-F monitoring is used to identify ischemic regions for the recognition of minor technical failures associated with ischemia and reperfusion experiments in the isolated perfused heart system. The visualization of NADH-F is possible by simply irradiating the heart with ultraviolet light. Rat hearts, in the working-heart mode, were subjected to occlusion/reperfusion of the left coronary artery, and analyzed. The perfusate was filtered through a 5 micron pore membrane. Out of 281 hearts which were judged to be free of technical failures by conventional physiological indices (heart rate greater than 200/min, cardiac output greater than 34 ml/min, and coronary flow 9-14 ml/min), 43 (15%) disclosed an abnormal NADH-F area prior to the coronary intervention. During coronary intervention, 29 technical failures were detected as indicated by sparse NADH-F distribution with occlusion, delayed disappearance of NADH-F upon reperfusion, or the exhibition of an abnormal NADH-F region unassociated with the coronary artery supply area. These technical failures are not detectable without the use of NADH-F, although the actual number of failures detected may depend on the skill of the operator. We recommend NADH-F monitoring for any preparations which do not contain hemoglobin, since NADH-F is an intrinsic probe for ischemia and is easily applicable to a variety of experiments.

Limitations in calculating left ventricular volume by two dimensional geometry--an exised canine heart study.

The left ventricle was removed from 76 dogs and was cast in silicone, in vitro, under three fixing pressure levels to simulate various end-diastolic pressures. This cast was designated as a silicone cast. The waxen cast was constructed by adding attachments which protrude inside the LV cavity, such as the papillary muscles and trabeculae carneae to the silicone cast. The cast volumes were compared with the volume calculated by the area-length method, including ellipsoid and paraboloid models, and by Chapman's method in which silhouettes of the silicone casts projected on 4 planes were used. Under a lower fixing pressure, the volume of papillary muscles and trabeculae carneae accounted for about 35% of the LV volume which was independent of either size of heart or weight of the dog. This ratio was reduced at higher fixing pressure levels. The relationship between the cast volume and the volume calculated by the silhouette method was linearly proportional. However, the deviation increased with higher fixing pressure levels and with larger ventricular volumes in all calculation methods, indicating the shape of the left ventricle cannot be represented by any ideal symmetrical spherical model. The calculated volume agreed with its corresponding cast volume with an error of less than 10% if either the fixing pressure level was below 5 mmHg, or the volume was less than 50 ml.

Long-term survival of a patient with Lutembacher's syndrome.

An elderly woman with Lutembacher's syndrome remained asymptomatic until the age of 55, when she was treated for exertional dyspnea with digitalis and diuretics. She died of gastrointestinal hemorrhage and hepatic failure at the age of 69. The autopsy revealed a large atrial septal defect and mitral stenosis without rheumatic changes. This patient is the oldest reported survivor of Lutembacher's syndrome with nonrheumatic mitral stenosis.