Effects of sildenafil citrate (Viagra) combined with nitrate on the heart.

BACKGROUND: Sildenafil citrate (Viagra) is indicated for the treatment of erectile dysfunction. Large and sudden decreases in systemic blood pressure were reported in a substantial number of patients taking sildenafil citrate combined with nitroglycerin. We studied the effect of sildenafil citrate on the relationship between changes in systemic blood pressure and coronary blood flow. METHODS AND RESULTS: Healthy male beagles were used to assess systemic blood pressure, pulmonary arterial pressure, and flow in the left circumflex artery (in which a critical stenosis was established) and left anterior descending coronary artery. After measurement of the hemodynamic variables, 2 mg/kg sildenafil citrate was administered via a nasogastric tube. Hemodynamic changes were monitored for 1 hour. Subsequently, the acute effect of nitrate combined with sildenafil citrate was studied by the bolus injection of 0.2 mg isosorbide dinitrate before and after sildenafil citrate. Systemic blood and pulmonary arterial pressures and circumflex flow did not change during this study; however, left anterior descending coronary arterial flow increased from 16.0+/-5.8 to 24.6+/-8.7 mL/min 1 hour after administration of sildenafil citrate. The prolongation of systemic blood pressure decrease and the circumflex flow decrement induced by isosorbide dinitrate after sildenafil citrate were significantly larger and longer than those before sildenafil citrate. CONCLUSIONS: Sildenafil citrate had the effect of vasodilation in a normal coronary artery; however, a combined effect with nitrate resulted in large and protracted decreases in systemic blood pressure and coronary blood flow in vessels with critical stenosis.

Plasma atrial natriuretic peptide response to direct current cardioversion of atrial fibrillation in patients with mitral stenosis.

OBJECTIVES: The purpose of this study was to evaluate the effect of direct current cardioversion therapy on the plasma concentration of atrial natriuretic peptide and to determine the main factors that influence the change in plasma atrial natriuretic peptide levels in patients with atrial fibrillation. BACKGROUND: In atrial arrythmias, whether the fast atrial rate itself or the associated elevation of atrial pressure, or both, contributes to the increase in atrial natriuretic peptide is a subject of debate. METHODS: In 15 patients with mild mitral stenosis, plasma atrial natriuretic peptide levels were measured and transmitral flow pattern was obtained by continuous wave Doppler echocardiography immediately before cardioversion and at 5 min, 4 h, 24 h and 5 days after direct current cardioversion. Mean mitral pressure gradient and atrial filling fraction were calculated on the basis of transmitral flow. RESULTS: In three patients who did not have a successful return to sinus rhythm, plasma atrial natriuretic peptide levels remained elevated after cardioversion. In 12 patients who maintained sinus rhythm, plasma atrial natriuretic peptide levels were significantly reduced from 79 +/- 29 to 36 +/- 11 pg/ml 4 h after cardioversion to sinus rhythm. However, the mitral pressure gradient did not change significantly during the observation period. There were progressive increases in atrial filling fraction throughout the observation period. From 4 h to 5 days after direct current cardioversion, plasma atrial natriuretic peptide levels gradually increased concomitantly with the recovery of atrial mechanical function. CONCLUSION: The reduction of plasma atrial natriuretic peptide levels after direct current cardioversion might be due to recovery from the high rate of atrial firing and not to an alteration in the mitral pressure gradient. Direct current cardioversion itself does not seem to influence atrial natriuretic peptide secretion. The increase in atrial natriuretic peptide levels from 4 h to 5 days after cardioversion concomitantly with an increase in atrial filling fraction may be due to recovery of atrial mechanical function.

Salutary effect of disopyramide on left ventricular diastolic function in hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The purpose of this study was to estimate the effect of disopyramide on left ventricular diastolic function in patients with hypertrophic obstructive cardiomyopathy. BACKGROUND: Although disopyramide has been reported to lessen clinical symptoms in patients with hypertrophic obstructive cardiomyopathy, few data exist regarding its effect on diastolic function in these patients. METHODS: Thirteen patients with hypertrophic cardiomyopathy (six with and seven without left ventricular outflow obstruction) were examined. Before and after intravenous disopyramide, hemodynamic and angiographic studies were performed. RESULTS: In patients with outflow obstruction, pressure gradient at the outflow tract decreased from a mean +/- SD of 100 +/- 45 to 26 +/- 33 mm Hg (p < 0.01). Although systolic function was similarly impaired in both groups, the time constant of left ventricular pressure decay (tau) shortened from 56 +/- 10 to 44 +/- 8 ms (p < 0.01) and the constant of left ventricular chamber stiffness (kc) decreased from 0.049 +/- 0.017 to 0.038 +/- 0.014 m2/ml (p < 0.01) only in patients with outflow obstruction. Shortening in tau correlated best with decrease in left ventricular systolic pressure (r = 0.84, p < 0.01). In contrast, tau was prolonged from 52 +/- 10 to 64 +/- 11 ms (p < 0.01) and kc was unchanged in patients without outflow obstruction. CONCLUSIONS: The primary effects of disopyramide on the hypertrophied left ventricle were negative inotropic and negative lusitropic. However, left ventricular diastolic properties in patients with outflow obstruction were improved with a decrease in outflow pressure gradient. Relief of clinical symptoms in hypertrophic obstructive cardiomyopathy with disopyramide might be due in part to improvement of diastolic function, which appears secondary to the reduction in ventricular afterload.

Different mechanisms of ischemic adaptation to repeated coronary occlusion in patients with and without recruitable collateral circulation.

OBJECTIVES: The aim of this study was to investigate the interaction between ischemic preconditioning (IP) and collateral recruitment (CR) during ischemic adaptation in patients. BACKGROUND: The mechanism of ischemic adaptation still remains controversial in humans. METHODS: The clinical, electrocardiographic, hemodynamic and echocardiographic responses to three 150-s occlusions of the left anterior descending coronary artery were assessed in relation to CR in 18 patients with effort angina undergoing elective percutaneous transluminal coronary angioplasty. RESULTS: During the first occlusion, recruitable collateral circulation (RCC) to the occluded myocardium was detected by myocardial contrast echocardiography in 6 patients (Group C) and was not seen in 12 (Group N). In Group N, all patients manifested signs of severe ischemia during each inflation. However, their symptoms and ST segment shift significantly decreased from the first to the third occlusions, suggesting the occurrence of IP. The elevation of mean pulmonary artery pressure and deterioration of anterior wall motion were comparable between the first and the third occlusions in Group N. In contrast, myocardial ischemia was significantly less marked during occlusion in Group C than in Group N, and no preconditioning effect was observed. The extent of RCC did not differ between the first and the third occlusions in each group. CONCLUSIONS: Both IP and CR may play independent roles in ischemic adaptation in humans. With RCC, myocardial ischemia was greatly reduced. Without RCC, preconditioning clinically and electrocardiographically lessened myocardial ischemia but failed to preserve left ventricular function.

Effects of percutaneous transvenous mitral commissurotomy on levels of plasma atrial natriuretic peptide during exercise.

To clarify the factors that influenced the secretion of human atrial natriuretic peptide (ANP) during exercise, we studied the relations between the changes in ANP, transmitral pressure gradient, heart rate and blood pressure at exercise in 16 patients with mitral stenosis before and after percutaneous transvenous mitral commissurotomy (PTMC). Before PTMC, ANP levels increased from 107 +/- 70 to 183 +/- 96 pg/ml during exercise testing (p less than 0.01), concomitant with the increment in mean transmitral pressure gradient, heart rate and systolic blood pressure. After PTMC, ANP levels also increased from 78 +/- 43 to 117 +/- 64 pg/ml, concomitant with the increment of those parameters. However, increments of ANP, mean transmitral pressure gradient and heart rate after PTMC were lower than those before PTMC. Because the most important factor influencing the secretion of ANP was unclear, the differences between these parameters were calculated at submaximal exercise before and after PTMC. There was a significant relation only between the change in ANP and mean transmitral pressure gradient (r = 0.70, p less than 0.01). These results suggest that the most important factor influencing the secretion of ANP during exercise is the change in transmitral pressure gradient in patients with mitral stenosis.

Left ventricular diastolic pressure-volume response immediately after successful percutaneous transvenous mitral commissurotomy.

The left ventricular (LV) diastolic pressure-volume response after percutaneous transvenous mitral commissurotomy (PTMC) was investigated to determine whether it was related to the baseline conditions of the left ventricle. Left ventriculography was performed, and the measurements of LV pressure were obtained in 32 patients before and after PTMC. Mitral valve area increased from 1.0 +/- 0.3 to 1.9 +/- 0.4 cm2 (p < 0.005) after PTMC, which caused a decrease in left atrial mean pressure (14.8 +/- 5.9 to 7.4 +/- 2.7 mm Hg; p < 0.005). LV end-diastolic pressure increased in all patients 5 minutes after PTMC. However, patients could be divided into 2 groups according to the following changes in LV end-diastolic pressure 20 minutes after PTMC: In 22 patients, LV end-diastolic pressure returned to the near-baseline level 20 minutes after PTMC (before 5.0 +/- 2.2, 5 minutes after 8.6 +/- 3.1, and 20 minutes after 6.3 +/- 2.5 mm Hg) with a significant increase in LV end-diastolic volume index (64 +/- 12 to 74 +/- 14 ml/m2; p < 0.001) and augmentation of LV stroke volume index (39 +/- 9 to 47 +/- 11 ml/m2; p < 0.001). However, in the remaining 10 patients with a larger LV volume (> 80 ml/m2) and reduced ejection fraction (< 50%) at baseline, LV end-diastolic pressure further increased 20 minutes after PTMC (before 5.5 +/- 2.8, 5 minutes after 7.8 +/- 2.7, and 20 minutes after 11.0 +/- 2.9 mm Hg) without significant changes in LV volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of myocardial contrast echocardiography and coronary angiography for assessing the acute protective effects of collateral recruitment during occlusion of the left anterior descending coronary artery at the time of elective angioplasty.

To assess the immediate change in collateral flow distribution within the occluded myocardium and the acute protective effects on myocardial ischemia after coronary occlusion, myocardial contrast echocardiography (MCE) was performed in 15 patients with normal left ventricular function undergoing elective coronary angioplasty of the left anterior descending artery, and the results were compared with those obtained from coronary angiography (CA). The sonicated or nonsonicated contrast material was injected into the right coronary artery before and during coronary occlusion and collaterals were graded on a 4-point scale (none = 0 to good = 3). Development of subjective anginal symptoms, ST-segment shift and wall motion abnormality during coronary occlusion were graded on a 4-point scale (none = 0 to severe = 3). Both MCE and CA detected a significant development in collateral flow during coronary occlusion. There was no significant correlation between MCE and CA collateral grades before or during coronary occlusion. The collateral flow assessed with MCE was inversely but significantly correlated with development of subjective anginal symptoms (r(s) = -0.70, p <0.01), ST-segment shift (r(s) = -0.78, p < 0.005) or wall motion abnormality (r(s) = -0.91, p < 0.001) during coronary occlusion. In contrast, the angiographic collateral flow was not correlated with development of anginal symptoms (r(s) = -0.46, p = 0.10), ST-segment shift (r(s) = -0.41, p = 0.14), or wall motion abnormality (r(s) = -0.26, p = 0.35). The present study suggested that the acute protective effects of coronary collaterals during coronary occlusion were closely associated with myocardial perfusion rather than the angiographic epicardial collateral vessel filling, and thus MCE was useful in assessing the acute protective effects of coronary collaterals during coronary occlusion.

Estimation of shunt flow in coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin.

The shunt flow from the coronary artery to pulmonary arteries was evaluated in 6 patients with coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin. In 2 patients, whose degree of visualization of pulmonary arteries by coronary angiography was relatively high, lung perfusion scintigrams demonstrated the defects at the distal of coronary-pulmonary fistulas.

Improvement in pulmonary function in mitral stenosis after percutaneous transvenous mitral commissurotomy.

Before and after percutaneous transvenous mitral commissurotomy (PTMC), pulmonary function studies were performed in 25 patients with mitral stenosis, in order to determine the effects of pulmonary hemodynamics on pulmonary function in patients with mitral stenosis. After PTMC, dramatic improvements in pulmonary hemodynamics were seen in all patients. With regard to pulmonary function data, the VC as percent predicted value increased from 87.6 +/- 16.1 percent to 94.7 +/- 14.4 percent (p less than 0.001). Although the ratio of FEV1/FVC was unchanged, the MVV as percent predicted value increased, and the ratio of RV/TLC, CV, and the difference in nitrogen concentration between 750 ml and 1,250 ml of expired volume decreased significantly. According to the maximum expiratory flow-volume curves, V ax 50% and Vmax 25% improved. Despite marked improvements in pulmonary ventilatory function soon after PTMC, the percent predicted diffusing capacity of the lung for carbon monoxide decreased significantly after PTMC. Arterial blood gas data, such as the partial pressure of oxygen and carbon dioxide in arterial blood and the alveolar-arterial differences in partial pressure of oxygen, did not improve within one or two weeks after PTMC. We conclude that in mitral stenosis, the majority of ventilatory function impairments are caused by hemodynamic alterations that are mainly reversible.

Early diagnosis of stuck Starr-Edwards disc valve in mitral position: inconstant and interrupted mitral regurgitation.

The patient was a 40-year-old man with Starr-Edwards disc valve for 21 years without symptoms. Newly developed systolic murmur at the apex was noticed at the monthly medical examination. Doppler color flow mapping indicated severe mitral regurgitation. However, the appearance of mitral regurgitation was not constant. Continuous wave Doppler recording indicated that some of the mitral regurgitations were abruptly terminated at early or mid systole with the disc closing signal. Mitral regurgitation was observed only at bradycardia and on the left lateral position. Cardiac surgery demonstrated no abnormality on the disc valve except small sulci on the rim of the disc. When the disc was tilted in the cage, it was stuck and did not move. Echocardiography was useful in detecting the early stage of stuck artificial valve that might be fatal in the mitral position.

Intraoperative application of power Doppler imaging: visualization of myocardial perfusion after anastomosis of left internal thoracic artery to left anterior descending coronary artery.

The purpose of this study was to determine the role of power Doppler imaging in assessing patency of coronary artery bypass graft (CABG) anastomosis. Twelve consecutive patients referred for CABG with the use of anastomosis of the internal thoracic artery to the left anterior descending coronary artery (LAD) were studied. A linear 6.5-MHz wide-band transducer was used during cardioplegic administration and reperfusion. Baseline power Doppler signals were obtained in the LAD in 11 patients, and post-CABG signals were obtained in 11 patients. In one patient the LAD was poorly visualized because of extensive calcification. In another patient the flow after bypass worsened and the graft was revised. Visualization of the LAD and internal thoracic artery grafts by epicardial intraoperative power Doppler imaging is feasible in almost all patients and allows rapid and simple intraoperative assessment of graft patency. In addition, myocardial perfusion is limited by heavily calcified coronaries.

Clinical application of power Doppler imaging to visualize coronary arteries in human beings.

Supplementation of angiographic information during bypass procedures is an attractive goal for the echocardiographic researcher. Compared with color flow mapping, power Doppler imaging is superior in terms of identifying small vessels and noise suppression because of the use of Doppler signal strength for imaging. Although power Doppler imaging does not provide information about flow velocity or its direction, it does show detailed vessel flow in a static organ. Our study was designed to obtain angiographic images of the coronary artery by the use of power Doppler imaging in 31 patients during open heart surgery. During cold cardioplegic infusion, the epicardial coronary artery and the coronary artery within myocardium, such as the septal perforator, could be well visualized by power Doppler imaging. There was good correlation between the diameters of coronary arteries measured from power Doppler imaging and those from quantitative coronary angiography (r = 0.964, p < 0.0001). We obtained clear and accurate images of the coronary artery by using power Doppler imaging during cardiac standstill. These images might provide meaningful supplemental information to the operator, such as confirming the target coronary artery during the cardioplegia and choosing the appropriate arterial portion for a bypass operation.

Dynamic change in collateral flow associated with myocardial ischemia in humans.

BACKGROUND: This study sought to investigate how collateral flow changes during myocardial ischemia in patients. METHODS: Myocardial contrast echocardiography (MCE) and rapid atrial pacing were performed in 20 patients with angiographically evidenced coronary collaterals from the right coronary artery (RCA) to the occluded left anterior descending coronary artery. Sonicated contrast medium was injected into the RCA before and immediately after atrial pacing to determine the peak background-subtracted contrast intensity (PI) in the collateral territory (PIA) and its ratio to PI in the control territory (PI ratio) as parameters of collateral blood flow. Lactate production in the coronary circulation during pacing was determined to assess myocardial ischemia in the collateral territory. RESULTS: PIA showed a significant correlation with regional wall motion either before (r(squared)=-0.64, P<0.01) or after pacing (r(squared)=-0.65, P<0.01). Similarly, PI ratio was significantly correlated with regional wall motion either before (r(squared)=-0.54, P<0.05) or after pacing (r(squared)=-0.64, P<0.01). Rapid atrial pacing decreased both PIA and PI ratio significantly greater in patients with lactate production than in those without (PIA: -67+/-53 vs. -15+/-34%, P<0.05; PI ratio: -68+/-49 vs. -8.2+/-32%, P<0.05, respectively), while neither PIA nor PI ratio differ between the two groups of patients before pacing (PIA: 13.8+/-19. vs. 16.2+/-13.3U, P=0.75; PI ratio: 0.70+/-0.71 vs. 0.87+/-0.65, P=0.58, respectively). CONCLUSIONS: We concluded that (1) collateral flow determined by MCE was closely associated with regional cardiac function, and (2) not the amount of collateral flow at rest, but pacing-induced change of collateral flow seemed to be a determinant of regional ischemia in patients with coronary collaterals.

Serial changes of mitral flow pattern after percutaneous transvenous mitral commissurotomy--assessment of Doppler and two-dimensional echocardiography.

To evaluate the acute change in the mitral flow pattern, especially pressure half-time after percutaneous transvenous mitral commissurotomy (PTMC) and to investigate the factors influencing the mitral flow pattern, Doppler and two-dimensional echocardiographic studies were performed in 15 patients before and two, six, 10 and 24 hours and seven days after PTMC. Mitral valve area increased and the mean mitral pressure gradient decreased after PTMC (1.0 +/- 0.4 cm2 to 1.8 +/- 0.4 cm2; 11 +/- 6 mmHg, to 3 +/- 2 mmHg, p < 0.01). Pressure half-time also decreased two hours after surgery, from 292 +/- 70 msec to 176 +/- 48 msec (p < 0.01) and then gradually decreased to 140 +/- 47 msec within seven days of the procedure without remarkable changes in mitral valve area and the mean transmitral pressure gradient. Left atrial dimensions decreased and left ventricular end-diastolic dimensions gradually increased after PTMC (51 +/- 6 mm to 46 +/- 5 mm; 47 +/- 4 mm to 50 +/- 3 mm). The time course of this was similar to that of the pressure half-time. Further study, in which the changes in pressure half-time were evaluated within 30 minutes of PTMC in 17 patients, indicated that pressure half-time significantly decreased from 248 +/- 69 msec to 139 +/- 28 msec five minutes after balloon inflation, slightly increasing again after 30 minutes to 153 +/- 31 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in peak oxygen uptake by restoration of atrial contraction in patients after percutaneous transvenous mitral commissurotomy.

The aim of the present study was to determine the effect of sinus conversion after mitral commissurotomy on the exercise performance of patients with mitral stenosis (MS) and atrial fibrillation (Af). Electric cardioversion was attempted 10 days after successful balloon mitral commissurotomy in 32 patients with MS and Af. Both symptom-limited exercise tests with respiratory gas analysis and constant workload exercise tests with echo-Doppler examinations were performed before, five days and three months after mitral commissurotomy, and five days after successful sinus conversion. The balloon commissurotomy attenuated the increase in transmitral pressure gradient during exercise. However, no significant increase either in peak oxygen uptake (PVO2) or stroke volume were observed even three months after commissurotomy in patients with persistent Af. Sinus conversion was successful in 17 patients and PVO2 increased from 21.4 +/- 4.1 to 23.4 +/- 4.0 ml/min/kg (p < 0.01). The extent of the increase in PVO2 was related to the atrial contribution in transmitral flow (R2 = 0.39, y = 0.81x + 1.2). Sinus rhythm was maintained for three months in 14 of 17 patients. Increased PVO2 was also preserved in these patients. These results suggest that the sinus conversion after mitral commissurotomy has an effect on the exercise performance of patients with MS and Af.

Mechanism for abnormal thallium-201 myocardial scintigraphy in patients with left bundle branch block in the absence of angiographic coronary artery disease.

Patients with left bundle branch block (LBBB) often show abnormal images on exercise thallium (T1)-201 scintigraphy without evidence of significant coronary stenosis. We investigated the mechanism for this phenomenon. Six patients with LBBB and without significant coronary stenosis underwent T1-201 SPECT, ECG-gated SPECT imaging with Tc-99m-methoxyisobutyl-isonitrile (MIBI), and atrial pacing stress test. The % count amplitude in Tc-99m-MIBI images was calculated as [(maximal counts) - (minimal counts)]/(minimal counts) x 100. Though all patients had a low count in the septal and inferior wall in T1-201 SPECT images, there was no ischemic production of lactate during an atrial pacing stress test. Nevertheless, gated SPECT images showed attenuated septal activity during systole. In patients with LBBB, the ratios of % count amplitude at the septum to that at the lateral wall at rest (0.47 +/- 0.05, mean +/- SE) were significantly less than the controls (n = 5, 0.83 +/- 0.12, p = 0.014). In conclusion, these results suggest that abnormal T1-201 SPECT images of the septum in patients with LBBB are partially caused by impaired septal wall thickening during systole. Such an abnormal wall motion may reduce blood flow demands to the septum, resulting in reduction of coronary blood flow with little ischemia.

[Initial and follow-up results of PTCA and PTMC].

On the bases of the initial and follow-up results of patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and percutaneous transvenous mitral commissurotomy (PTMC), the proper applications of these interventional therapies were discussed. The efficacy of PTMC on valvotomy was comparable to open mitral commissurotomy and the procedural safety was noticed. Our results supported the use of PTMC for patients with plicable mitral valve. Despite the good and acceptable results of elective PTCA, low initial success rate and high incidence of major cardiac events including mortality was noted in the group of urgent PTCA for patients with multivessel lesions. The urgent use of PTCA for refractory unstable angina should be restricted to selected patients without high-risk multivessel lesions.

[Drug induced impotence].

Medication induced impotence has been reported in the some papers. However, it is unusual to talk about the sexual history in a general clinical interview and there are few reports to show the possible mechanisms of induced sexual dysfunction in Japan. Recently, the average life span of the Japanese population has gradually increased, so now we have a chance to evaluate the sexual history from older people. Some drugs, such as diuretics, antiarrtythmic and antihypertensive drugs, were reported to induce impotence, however, there was not a detailed study in Japan. We studied the effect of cardiovascular medicine to sexual dysfunction in 1,000 patients. Almost all medication did not always reduce sexual activities, however, sexual activities in old people might decrease because of medications or sickness. It is important for the general physician to ask the patients about general conditions including sexual history while on medications.