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.

[Effect of oxygen inhalation on myocardial opacification using levovist: an animal experimental study].

OBJECTIVES: Levovist can opacify the myocardium via venous injection, and is widely used in the clinical field. However, left ventricular opacification deteriorates during oxygen inhalation using Albunex, one of the first generation of contrast agents. This study examines the effect of blood oxygen pressure on the myocardial opacification by Levovist. METHODS: Myocardial contrast echocardiography (Toshiba Power Vision 6000) was performed using second harmonic imaging, intermittent exposure of ultrasound (every 4 cardiac beats) and acoustic power of 1.4 mechanical index. The video intensity of the ventricular septum after venous injection of Levovist (0.5 ml of 300 mg/ml) was measured under various respiratory conditions by manipulating the respirator and oxygen inhalation. Arterial blood gas was measured and correlated with the myocardial video intensity. RESULTS: The video intensity of myocardial opacification was lower with higher oxygen pressure in the arterial blood. Visual recognition of myocardial opacification was only 14% under high oxygen pressure over 200 mmHg. Microbubbles of Levovist form from normal air, and are easily affected by the gas concentration of the surrounding blood. CONCLUSIONS: Myocardial opacification using Levovist is deteriorated under high oxygen pressure at examination.

[Optimal setting of focus points for myocardial contrast echocardiography with intravenous Optison (FS-69): an experimental study].

OBJECTIVES: Myocardial contrast echocardiography is useful to assess myocardil perfusion, but myocardial opacification is affected by the setup of the ultrasonic equipment. The optimal setting of focus points for adequate opacification of the myocardium was examined in myocardial contrast echocardiography. METHODS: Myocardial contrast echocardiography was performed in six dogs using triggered second harmonic technology following intravenous administration of Optison(FS-69). The short-axis view was recorded and baseline subtracted video intensity(peak intensity: PI) was calculated at three regions of the left ventricular wall, the anterior, septum, and posterior walls, to evaluate myocardial opacification. The focus point was set at near(2 cm), middle(4 cm) and far(6 cm)points. The myocardial opacification was evaluated at each focus setting. The effect of the acoustic power was also examined by changing the mechanical index to 1.6, 1.2 or 0.8. RESULTS: Myocardial opacification was recognized at all focus points, and segments near the focus points had high PI. However, the PI of the posterior wall was lowest at near focus, whereas the PI of the anterior wall was lowest at far focus. The difference of PI between the anterior and posterior walls was significant (p < 0.05, p < 0.01, respectively) at either focus point. Adequate myocardial opacification of all segments was observed when the focus was set at the middle point. The PI of the whole left ventricle increased relative to mechanical index. CONCLUSIONS: Setting up of focus points at the middle of the left ventricle provides more homogeneous myocardial opacification of the whole left ventricle in myocardial contrast echocardiography, and high acoustic power possibly improves myocardial opacification. Inadequate setting of focus points leads to inadequate estimation of myocardial perfusion by myocardial contrast echocardiography.

[Usefulness of intravenous myocardial contrast echocardiography in rats].

OBJECTIVES: Few intravenous myocardial contrast echocardiography trials have evaluated myocardial perfusion in small animals. The feasibility of using intravenous myocardial contrast echocardiography to assess the ischemic area in rats was investigated. METHODS: Fourteen open chest Wister male rats were examined. Intravenous myocardial contrast echocardiography was performed by fundamental and intermittent mode using a high frequency (5-12 MHz) transducer (SONOS 5500) with injection of NC100100 (20% dilution) into the femoral vein. The mechanical index was set to 1.6. Baseline-subtracted video intensity (256 level) was measured in the anterior, posterior, septal and lateral walls of the left ventricle. The left anterior descending artery was ligated in 16 rats. The area at risk was evaluated by myocardial contrast echocardiography and compared to the area of defect by Evans Blue staining. RESULTS: All wall segments were clearly opacified (anterior 63.8 +/- 24.7, posterior 27.0 +/- 11.0, septal 44.5 +/- 11.6, lateral 52.3 +/- 19.1), although the baseline-subtracted video intensity of the posterior wall was low. The area at risk was clearly observed, and there was a good correlation with the nonperfused area by Evans Blue staining (y = 1.13x-3.54, r = 0.98). CONCLUSIONS: Intravenous myocardial contrast echocardiography can detect the perfusion defect even in rats using a high frequency transducer and suitable setup of equipment.

Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in in vivo myocardium of rats.

There have been many studies concerning the hemodynamics and physiological mechanisms in ischemic heart disease, little is known about molecular mechanisms during myocardial ischemia in in vivo study. As the signal transduction pathway responsible for myocardial hypertrophy and apoptosis, janus kinase (JAK) and signal transducers and activators of transcription (STAT) are suggested to play an important role. However, whether in vivo activation of JAK-STAT pathway occurs during myocardial ischemia is still unknown. The purpose of this study was to determine whether myocardial JAK or STAT is activated in ischemic heart, and to evaluate the angiotensin blockade on the pathway. Myocardial infarction was produced by ligation of the coronary artery in Wistar rats. After myocardial ischemia, we analysed both activated levels and total amounts of JAK1, JAK2, STAT1 and STAT3 by Western blot analyses at 0, 5, 15, 30, 60, 120 and 240 min. Compared with JAK activities at 0 min, JAK1 activities were significantly increased at 60 and 120 min (3.0- and 3.7-fold, respectively, P<0.01). JAK2 and STAT1 activities of ischemic myocardium were unchanged through the time course. STAT3 activities were increased at 5 min (3.3-fold, P<0.01) and markedly enhanced at 30, 60 and 120 min (4.6-, 7.7- and 8.7-fold, respectively, P<0.01). Pretreatment with imidapril (ACE inhibitor) and candesartan cilexitil (AT1 receptor antagonist) significantly prevented the increase in the phosphorylation of JAK1 at 120 min and STAT3 at 30 and 120 min. Sis-inducing factor (SIF) DNA complex was supershifted by specific anti-STAT3 antibody, indicating that increased SIF complex at least contained activated STAT3 proteins in ischemic myocardium. Imidapril and candesartan cilexitil inhibited the activation of SIF DNA binding at 1 day after coronary ligation. In conclusion, we showed that JAK1 and STAT3 were activated by ischemia from the basal activities in in vivo rat myocardial ischemia model. Imidapril and candesartan cilexitil prevented the increase in phosphorylated JAK1 and STAT3, thereby suggesting that angiotensin II, especially angiotensin II type I receptor, partially mediates activation of myocardial JAK-STAT pathway in acute myocardial ischemia.

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.

The role of coenzyme Q10 in the pathophysiology and therapy of experimental congestive heart failure in the dog.

BACKGROUND: Coenzyme Q10 (CoQ10) is essential for ATP generation and has antioxidant properties. Decreased CoQ10 levels have been reported in human heart failure (CHF), but it remains unclear if this is a conserved feature of CHF. The objective of the study was to determine if tachycardia-induced CHF in the dog is associated with reduced CoQ10 levels. Furthermore, it was hypothesized that CoQ10 supplementation may improve CHF severity by preventing CoQ10 deficiency (if present) or via antioxidant effects. METHODS AND RESULTS: Serum and myocardial levels of CoQ10 were examined in normal dogs (n = 6), dogs with CHF (control, n = 5), and dogs with CHF treated with CoQ10 (CoQ10; 10 mg/kg/day, n = 5). Serum CoQ10 levels did not change with CHF in control dogs, and myocardial levels were similar to those of normal dogs. CoQ10 therapy increased serum but not myocardial levels of CoQ10. In early CHF, CoQ10-treated dogs had lower filling pressures, and, in severe CHF, CoQ10-treated dogs had less hypertrophy as compared with untreated dogs. Other indices of CHF severity were similar in control and CoQ10-treated dogs. CONCLUSION: These data indicate that CoQ10 deficiency is not present in this model of CHF. Although dramatic effects on hemodynamics were not observed, CoQ10 supplementation did appear to attenuate the hypertrophic response associated with CHF. Key words: enzymes, cardiomyopathy, hormones, antioxidant.

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.

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.

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.

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.

[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.

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.

Salutary effect of adjunctive intracoronary nicorandil administration on restoration of myocardial blood flow and functional improvement in patients with acute myocardial infarction.

Salutary effect of nicorandil, a K+ adenosine triphosphate channel opener, on restoration of myocardial blood flow and functional improvement after coronary revascularization was investigated in 20 patients with first anterior acute myocardial infarction. Ten patients received intracoronary administration of nicorandil (2 mg) after coronary revascularization; the other 10 patients received coronary revascularization only and served as control subjects. Myocardial contrast echocardiography and two-dimensional echocardiography were performed to assess microvascular integrity and regional function in the infarcted area. Nicorandil improved peak contrast intensity ratio (p < 0.001), calculated as the ratio of peak contrast intensity in the infarcted and noninfarcted areas, indicating the restoration of myocardial blood flow to the infarcted myocardium. Regional wall motion improved more significantly in 1 month in patients who received nicorandil (p < 0.01). Thus our results suggested the usefulness of intracoronary nicorandil administration after coronary revascularization for restoring blood flow and functional improvement in patients with acute myocardial infarction.

Disappearance of the 'no-reflow' phenomenon after adjunctive intracoronary administration of nicorandil in a patient with acute myocardial infarction.

Adjunctive intracoronary administration of nicorandil, an ATP-sensitive potassium channel opener, after successful coronary revascularization was performed in a 54-year-old patient with acute myocardial infarction. The 'no-reflow' phenomenon disappeared after nicorandil administration and significant functional recovery of the infarcted myocardium was achieved. This suggests that nicorandil could eliminate the 'no-reflow' phenomenon after successful coronary revascularization.

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.