Effect of skin antiseptic solutions on the incidence of catheter-related bloodstream infection: a systematic review and network meta-analysis.

BACKGROUND: The most effective skin antiseptic solution to reduce the incidence of catheter-related bloodstream infections (CRBSI) remains unknown. AIM: To compare solutions with different chlorhexidine (CHG)-based concentrations and povidone-iodine (PVI) in adults with a central venous catheter (CVC) or arterial catheter, and identify an association with the incidence of CRBSI. METHODS: This study evaluated randomized controlled trials comparing CHG and PVI antiseptic agents in patients aged ≥18 years with an underlying illness and a CVC or arterial catheter. The primary outcome was CRBSI rate. Network meta-analysis was performed by a frequentist-based approach with multi-variate random effects meta-analysis, and the effect size was expressed as relative risk (RR) with 95% confidence interval (CI). FINDINGS: The search yielded 1511 records, of which five studies (2815 catheters) were included in the network meta-analysis. The risk of CRBSI was significantly lower with 1% CHG-alcohol than with 0.5% CHG-alcohol (RR 0.40, 95% CI 0.16-0.98; high certainty) or 10% PVI-aqueous (RR 0.31, 95% CI 0.15-0.63; high certainty). There was no significant difference in the risk of CRBSI between 1% CHG-alcohol and 2% CHG-aqueous (RR 0.35, 95% CI 0.12-1.04; moderate certainty) or other antiseptic solutions. The hierarchy of efficacy in reducing CRBSI was 1% CHG-alcohol, 0.5% CHG-alcohol, 2% CHG-aqueous and 10% PVI-aqueous. CONCLUSION: Antiseptic agents containing 1% CHG-alcohol were more strongly associated with reduced risk for CRBSI compared with agents containing 0.5% CHG-alcohol or 10% PVI-aqueous.

Quantitative ultrasonic tissue characterization can identify high-risk atherosclerotic alteration in human carotid arteries.

BACKGROUND: Recently, ultrasonic tissue characterization of the composition of plaques has been performed in a quantitative fashion on the basis of integrated backscatter (IBS) analysis, but most of those studies have used high-frequency ultrasound to obtain microscopic images. METHODS AND RESULTS: We performed B-mode measurement and IBS signal analysis with acoustic densitometry with a 7.5-MHz linear-array transducer in freshly excised human aortas (n=58) (normal, atheromatous, and fibrous tissue) obtained at autopsy. Atheromatous and fibrous tissue had a similar intima-media thickness (IMT), but the IBS value in atheromatous specimens was lower than that in fibrous specimens. We further applied this method to human carotid ultrasonography. The subjects were young (80 regions), middle aged with 1 or no coronary risk factors (low risk) (120 regions), middle aged with >/=2 coronary risk factors (high risk) (240 regions), or elderly (80 regions) or were patients with myocardial infarction (MI) with multivessel disease (90 regions). The IMT was similar in middle-aged, elderly, and MI subjects. In contrast, the IBS value was significantly higher in elderly subjects and lower in high-risk middle-aged and MI subjects compared with that in low-risk middle-aged subjects. The percent of regions diagnosed as atheromatous (IBS less than mean minus 2-SD value of IBS in young subjects) was 11% in low-risk middle-aged subjects, 29% in high-risk middle-aged subjects, and 63% in the MI group. CONCLUSIONS: In conjunction with conventional B-mode imaging, IBS analysis with carotid ultrasonography appeared to provide prognostic information to identify a high-risk group with systemic atherosclerosis, which could lead to coronary heart disease in individuals with early-stage disease.

Calcineurin inhibitor attenuates left ventricular hypertrophy, leading to prevention of heart failure in hypertensive rats.

BACKGROUND: There is controversy regarding the contribution of calcineurin activation to the development of pressure-overload left ventricular (LV) hypertrophy and heart failure. The aim of this study was to explore whether the inhibition of calcineurin may prevent the transition to heart failure in hypertensive rats and, if so, to clarify in which developmental stage of LV hypertrophy calcineurin plays a key role. METHODS AND RESULTS: Dahl salt-sensitive rats placed on an 8% NaCl diet from the age of 7 weeks (hypertensive rats) were randomized to no treatment (n=6) or treatment with the calcineurin inhibitor FK506 (1 mg x kg(-1) x d(-1)) from 8 weeks (FKE, n=7) or from 17 weeks (FKL, n=7). Rats placed on a 0.3% NaCl diet were defined as control rats (n=6). The administration of FK506 from 8 weeks attenuated, although it did not block, LV hypertrophy observed in the untreated rats and prevented the transition to heart failure. The development of LV fibrosis, however, was not attenuated by the administration of FK506 from 8 weeks. The administration of FK506 from 17 weeks brought no benefit for cardiac remodeling or LV function and failed to prevent heart failure. CONCLUSIONS: Calcineurin inhibition, if started from the initial stage of pressure overload, attenuated the development of LV hypertrophy without any effect on LV fibrosis and prevented the transition to heart failure. The activation of calcineurin is involved in the development of LV hypertrophy but not of LV fibrosis, and this involvement may be crucial at the initial stage.

Effects of changes in coronary stenosis on left ventricular diastolic filling assessed with pulsed Doppler echocardiography.

To determine the effects of changes in coronary stenosis on left ventricular diastolic filling, diastolic filling was serially examined before and after percutaneous transluminal coronary angioplasty using pulsed Doppler echocardiography in 50 patients with stable exertional angina pectoris. Peak rapid filling velocity and the ratio of peak atrial filling to peak rapid filling velocities were measured from the transmitral flow velocity pattern before and 2 and 9 days after coronary angioplasty. Peak rapid filling velocity increased and the ratio of peak atrial filling to peak rapid filling velocities decreased gradually after coronary angioplasty. The improvement in left ventricular diastolic filling was greater in patients with severe (greater than 90%) coronary stenosis than in patients with mild (less than or equal to 90%) coronary stenosis. In the long-term follow-up period, the improved left ventricular diastolic filling worsened in only 11 patients with marked progression to greater than 90% coronary stenosis. Thus, left ventricular diastolic filling improved gradually after coronary angioplasty, possibly reflecting post-ischemic "stunned" myocardium. Serial examinations of left ventricular diastolic filling with pulsed Doppler echocardiography may be a means of noninvasively assessing the temporal changes in the coronary stenosis and predicting the occurrence of coronary restenosis after coronary angioplasty.

Effects of nitroprusside on transmitral flow velocity patterns in extreme heart failure: a combined hemodynamic and Doppler echocardiographic study of varying loading conditions.

To explore the mechanisms of change of left ventricular diastolic filling associated with preload and afterload reduction, the influence of nitroprusside on the transmitral flow velocity pattern, pulmonary capillary wedge pressure and left ventricular pressure interaction was studied in 11 patients with end-stage heart failure. Pulsed Doppler echocardiographic recordings of mitral inflow were obtained with simultaneous high fidelity left ventricular and phase-corrected pulmonary capillary wedge pressure recordings before and during levels of nitroprusside infusion. With nitroprusside, left ventricular systolic and end-diastolic pressures decreased by 14% and 41% (p less than 0.05, p less than 0.05), respectively, and cardiac output increased by 67% (p less than 0.05). The pulmonary capillary wedge-left ventricular crossover pressure decreased by 41% (p less than 0.05), but the time constant of isovolumetric left ventricular pressure decrease T was insignificantly changed. Isovolumetric relaxation time and acceleration and deceleration times of the early diastolic filling wave were significantly prolonged with nitroprusside infusion (p less than 0.05, p less than 0.05 and p less than 0.05, respectively). Peak early diastolic filling velocity was maintained (65 +/- 11 to 62 +/- 13 cm/s, p = NS) in spite of the decreased absolute crossover pressure. Changes in peak early diastolic filling velocity correlated weakly with changes in the crossover pressure (r = 0.48, p less than 0.05) and correlated better with the crossover to left ventricular minimal pressure difference (r = 0.78, p less than 0.05). Peak early diastolic filling velocity appears to be most affected by the early diastolic pulmonary capillary wedge to left ventricular pressure difference rather than the absolute pulmonary capillary wedge pressure. The lack of peak flow velocity change during nitroprusside infusion could be explained by either the associated decrease in left ventricular minimal pressure or downward shift of left ventricular diastolic pressure by the same amount as the decrease in pulmonary capillary wedge pressure. This may reflect a reduction of external constraint to ventricular distensibility produced by a reduction in filling volume in patients with a markedly dilated ventricle. Thus, a prolonged early diastolic filling period and preserved peak early diastolic filling velocity in spite of decreased left ventricular filling pressure and constant relaxation rate are associated with the beneficial effects of nitroprusside on left ventricular function in patients with severe congestive heart failure.

Right coronary artery occlusion: its role in the mechanism of precordial ST segment depression.

To investigate the mechanism of precordial ST segment depression during right coronary artery occlusion, precordial ST segment shifts and myocardial lactate metabolism were evaluated during coronary angioplasty in 10 patients with (group A) and 7 patients without (group B) precordial ST segment depression during balloon occlusion of the right coronary artery, and in 17 patients with precordial ST segment depression during balloon occlusion of the left anterior descending artery (group C). A 12 lead electrocardiogram was continuously recorded in each patient. Blood lactate in the aorta and great cardiac vein was measured during the procedure, and the lactate extraction ratio in the anterior wall was determined both before and during balloon occlusion. Eight of the 10 patients in group A and 1 of the 7 patients in group B had a dominant large right coronary artery. There were no significant differences in summed ST segment elevation in leads II, III and a VF between group A (0.56 +/- 0.26 mV) and group B (0.46 +/- 0.19 mV) during balloon occlusion of the right coronary artery, and no significant differences in summed ST segment depression in leads V1 to V6 during balloon occlusion between group A (0.44 +/- 0.26 mV) and group C (0.38 +/- 0.14 mV). Lactate extraction ratio before balloon occlusion was similar among the three groups. Patients in group A had a higher lactate extraction ratio during (38 +/- 11%) compared with before (30 +/- 11%) (p less than 0.05) balloon occlusion despite precordial ST segment depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasonic tissue characterization with a real time integrated backscatter imaging system in normal and aging human hearts.

Experimental studies have shown that variation in the magnitude of integrated ultrasonic backscatter during the cardiac cycle represents acoustic properties of myocardium that are affected by pathologic processes; however, there are few clinical studies using integrated backscatter. Forty subjects without cardiovascular disease (aged 22 to 71 years, mean 41) were studied with use of a new M-mode format integrated backscatter imaging system to characterize the range of cyclic variation of integrated backscatter in normal subjects. Cyclic variation in integrated backscatter was noted in both the septum and the posterior wall in all subjects. The magnitude of the cyclic variation of integrated backscatter and the interval from the onset of the QRS wave of the electrocardiogram to the minimal integrated backscatter value were measured using an area of interest of variable size for integrated backscatter sampling and a software resident in the ultrasound scanner. The magnitude of cyclic variation was larger for the posterior wall than for the septum (6.3 +/- 0.8 versus 4.9 +/- 1.3 dB, p less than 0.01). The interval to the minimal integrated backscatter value was 328 +/- 58 ms for the septum and 348 +/- 42 ms for the posterior wall (p = NS). There was a weak correlation between the magnitude of cyclic variation of integrated backscatter and subject age for the posterior wall (r = -0.47, p less than 0.01), but this was not significant for the septum (r = -0.21) (partially because of inability to exclude specular septal echoes) and septal endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term administration of amlodipine prevents decompensation to diastolic heart failure in hypertensive rats.

UNLABELLED: OBJECTIVES; We assessed the effects of long-term amlodipine administration in a diastolic heart failure (DHF) rat model with preserved systolic function as well as the relationship between changes in left ventricular (LV) myocardial stiffening and alterations in extracellular matrix. BACKGROUND: Although the effect of long-term administration of amlodipine has been shown to be disappointing in patients with systolic failure, the effect is unknown in those with DHF. METHODS: Dahl salt-sensitive rats fed a high-salt diet for seven weeks were divided into three groups: eight untreated rats (DHF group), eight rats given high-dose amlodipine (10 mg/kg/day; HDA group) and seven rats given low-dose amlodipine (1 mg/kg/day; LDA group). RESULTS: High-dose administration of amlodipine decreased systolic blood pressure and controlled excessive hypertrophy, without a decrease in the collagen content, and prevented the elevation of LV end-diastolic pressure at 19 weeks. Low-dose administration of amlodipine with subdeppressive effects did not control either hypertrophy or fibrosis; however, it prevented myocardial stiffening and, hence, the elevation of LV end-diastolic pressure. The ratio of type I to type III collagen messenger ribonucleic acid levels was significantly lower in both the HDA and LDA groups than in the DHF group. CONCLUSIONS: Long-term administration of amlodipine prevented the transition to DHF both at the depressor and subdepressor doses. Amlodipine did not decrease the collagen content, but attenuated myocardial stiffness, with inhibition of the phenotype shift from type III to type I collagen. Thus, amlodipine may exert beneficial effects through amelioration of collagen remodeling in the treatment of DHF.

Evolving changes in Doppler mitral flow velocity pattern in rats with hypertensive hypertrophy.

OBJECTIVES: The aim of our study was to explore evolving changes in a mitral flow velocity pattern (MFVP) and its hemodynamic and pathological correlates in hypertensive rats in an isolated diastolic heart failure model. BACKGROUND: Development of left ventricular (LV) hypertrophy and concomitant diastolic dysfunction cause heart failure in hypertensive hearts even with normal systolic function; however, associated evolving change in MFVP is still unclear. METHODS: Mitral flow velocity pattern was recorded every 2 weeks from 7 to 19 weeks in six hypertensive rats. Hemodynamic and pathological correlates of Doppler mitral flow indexes were examined as an additional part of the study using the hypertensive rats at the age of 13 weeks (compensatory stage, n = 7) and at 19 weeks (heart failure stage, n = 8). RESULTS: Initial development of pressure overload LV hypertrophy resulted in a decrease in early diastolic filling wave (E), a reciprocal increase in the filling wave due to atrial contraction (A) and prolongation of deceleration time of E wave (relaxation abnormality pattern). These changes were associated with an increase in tau, an index of LV relaxation, but without a change in LV end-diastolic pressure. Transition to congestive heart failure caused an increase in E, a decrease in A and shortening of deceleration time. These changes were not associated with further increase in tau but with elevation of LV end-diastolic pressure, reflecting marked LV hypertrophy and myocardial fibrosis. CONCLUSIONS: Development of pressure overload LV hypertrophy is associated with evolving changes in MFVP from normal to relaxation abnormality pattern and, in turn, to pseudonormalized to restrictive pattern. Analysis of MFVP may be useful to follow not only functional but also constitutional changes of the myocardium in hypertensive hearts.

Analysis of transmural trend of myocardial integrated ultrasound backscatter for differentiation of hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension.

OBJECTIVES: This study was undertaken to differentiate hypertrophic cardiomyopathy from hypertensive hypertrophy using a newly developed M-mode format integrated backscatter imaging system capable of calibrating myocardial integrated backscatter with the power of Doppler signals from the blood. BACKGROUND: Myocardial integrated ultrasound backscatter changes in patients with hypertrophic cardiomyopathy; however, it is unknown whether ultrasound myocardial tissue characterization may be useful in differentiating hypertrophic cardiomyopathy from hypertensive hypertrophy. METHODS: Calibrated myocardial integrated backscatter and its transmural gradient were measured in the septum and posterior wall in 31 normal subjects, 13 patients with hypertensive hypertrophy and 22 patients with hypertrophic cardiomyopathy. The gradient in integrated backscatter was determined as the ratio of calibrated integrated backscatter in the endocardial half to that in the epicardial half of the myocardium. RESULTS: Cyclic variation of integrated backscatter was smaller and calibrated myocardial integrated backscatter higher in patients with hypertrophied hearts than in normal subjects, but there were no significant differences in either integrated backscatter measure between patients with hypertensive hypertrophy and those with hypertrophic cardiomyopathy. Transmural gradient in myocardial integrated backscatter was present only in patients with hypertrophic cardiomyopathy (5.0 +/- 1.8 dB [mean +/- SD] for the septum; 1.2 +/- 1.6 dB for the posterior wall). CONCLUSIONS: Hypertrophic cardiomyopathy and ventricular hypertrophy due to hypertension can be differentiated on the basis of quantitative analysis of the transmural gradient in integrated backscatter.

Dobutamine stress echocardiography predicts reversible dysfunction and quantitates the extent of irreversibly damaged myocardium after reperfusion of anterior myocardial infarction.

OBJECTIVES: This study was designed to evaluate dobutamine stress echocardiography in identifying reversible dysfunction and assessing the extent of irreversibly damaged myocardium early in acute myocardial infarction. BACKGROUND: Several experimental and clinical studies have suggested that dobutamine enhances contractile function of stunned or hibernating, or both, myocardium. It is important for clinical strategy to predict the magnitude of improvement in myocardial function early in acute myocardial infarction. METHODS: We studied 21 patients with a reperfused first anterior myocardial infarction. Two-dimensional echocardiography was performed before and during dobutamine infusion (10 micrograms/kg body weight per min) at a mean of 3 days after the infarction. Follow-up echocardiography was performed at a mean of 25 days later. To assess segmental wall motion, we divided the left ventricle into 17 segments and assigned a wall motion abnormality score: 3 = dyskinesia or akinesia; 0 = normal. Improvement in wall motion was indicated by a decrease of at least one grade in segmental score. For quantitative assessment, the ratio of endocardial length showing dyskinesia or akinesia to a left ventricular endocardial length (akinetic length ratio) was determined in the apical long-axis view at each stage. RESULTS: Sensitivity and specificity of dobutamine infusion in detecting improvement in wall motion at follow-up echocardiography were 83% (55 of 66 segments) and 86% (43 of 50 segments), respectively. Excellent correlation was found (r = 0.93, p < 0.001; absolute difference [mean +/- SD] 0.03 +/- 0.05) between the akinetic length ratios measured during dobutamine infusion and in the late convalescent stage. CONCLUSIONS: In the early stage of acute myocardial infarction, low dose dobutamine stress echocardiography provides a useful method for predicting reversible dysfunction with excellent sensitivity and specificity and can also be used to quantitate the extent of irreversibly damaged myocardium.

Importance of left ventricular minimal pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction.

OBJECTIVES: This study was designed to assess whether the transmitral flow velocity pattern provides an estimation of left atrial pressure irrespective of the presence of left ventricular systolic dysfunction and, if not, to clarify the mechanism. BACKGROUND: The pulsed Doppler transmitral flow velocity pattern, particularly peak early diastolic filling velocity, has been shown to change in parallel with left atrial pressure. However, extremely elevated left atrial pressure in association with heart failure does not necessarily cause an increase in peak early diastolic filling velocity in patients. METHODS: Left atrial pressure was elevated with intravenous saline infusion in 11 dogs (normal left ventricular function group) and hemodynamic, transesophageal Doppler echocardiographic and M-mode echocardiographic variables were recorded at three different loading levels. In another 12 dogs, left atrial pressure was elevated by production of left ventricular systolic dysfunction with the stepwise injection of microspheres into the left coronary artery (left ventricular dysfunction group) and the same set of recordings was obtained at three different levels of dysfunction. RESULTS: Peak early diastolic filling velocity increased with left atrial pressure in the normal left ventricular function group and correlated with mean left atrial pressure (r = 0.61, p < 0.01) and early diastolic left atrial to left ventricular crossover pressure (r = 0.71, p < 0.01). In contrast, peak early diastolic filling velocity did not increase with left atrial pressure in the left ventricular dysfunction group and did not correlate with mean left atrial pressure (r = -0.05) or the crossover pressure (r = 0.06). Peak early diastolic filling velocity correlated well with the difference between the crossover pressure and left ventricular minimal pressure in the left ventricular dysfunction group (r = 0.64, p < 0.01). In contrast to peak early diastolic filling velocity, deceleration time of the early diastolic filling wave correlated with mean left atrial pressure and the crossover pressure irrespective of the primary cause of preload alteration (r = -0.54, r = -0.59, p < 0.01 respectively, n = 69 for all data). CONCLUSIONS: Preload dependency of the Doppler transmitral flow velocity pattern is hampered if an increase in left atrial pressure is due to left ventricular systolic dysfunction. In this setting, the increase in left ventricular minimal pressure due to left ventricular systolic dysfunction cancels the effect of the increase in left atrial pressure on the flow velocity pattern.

Abnormal coronary flow dynamics at rest and during tachycardia associated with impaired left ventricular relaxation in humans: implication for tachycardia-induced myocardial ischemia.

OBJECTIVES: This study attempted to clarify the effect of ventricular relaxation abnormalities on coronary flow dynamics at rest and during tachycardia in humans. BACKGROUND: Ventricular relaxation abnormality has been demonstrated in animals to have an adverse impact on early diastolic coronary flow dynamics. However, this relation has not been established in humans. Even if the adverse effect were latent at rest, it might become evident during tachycardia because tachycardia reduces coronary flow reserve and facilitates the production of myocardial ischemia. METHODS: Doppler phasic left coronary flow velocity pattern was obtained at rest and during tachycardia in 23 patients without coronary stenosis. The time constant of left ventricular isovolumic pressure (tau) was used to assess ventricular relaxation. RESULTS: The time to peak flow velocity of the diastolic coronary flow wave was longer, and the fraction of the first third of diastolic coronary flow was smaller, in patients with a longer tau (r = 0.58, p < 0.01; r = -0.44, p < 0.05), indicating a close relation between early diastolic coronary flow dynamics and ventricular relaxation. Although rapid atrial pacing yielded an increase in the coronary flow velocity integral per minute in all patients, diastolic coronary flow velocity integral per minute increased in 9 patients with a normal (< or = 40 ms) tau at rest but decreased in 14 patients with a longer (> 40 ms) tau at rest. CONCLUSIONS: Impaired left ventricular relaxation was associated with decreased coronary flow in early diastole at rest and decreased coronary flow throughout diastole during tachycardia in patients without coronary stenosis. These findings may provide more insight into the mechanism of tachycardia-induced subendocardial ischemia in patients with impaired ventricular relaxation but without concomitant coronary stenosis.

Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction.

OBJECTIVES: We assessed the acute effect of intracoronary injection of verapamil on microvascular function after primary percutaneous translumanal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) with myocardial contrast echocardiography (MCE) in relation to functional outcomes. BACKGROUND: Recent clinical studies have documented the potential of verapamil for possible increase in coronary blood flow after primary PTCA. METHODS: Forty patients with a first AMI were randomly assigned to the verapamil group (n = 20) or the control group (n = 20). In the verapamil group, verapamil (0.5 mg) was injected into the infarct-related artery shortly after PTCA, followed by the oral administration. We performed MCE with an intracoronary injection of sonicated microbubbles before and after verapamil. To assess microvascular integrity, we determined the baseline-subtracted peak intensity in the risk area and the ratio of the no reflow zone plus the low reflow zone to the risk area (low reflow ratio). We determined the average wall motion score (dyskinesia/akinesia = 3; normal = 0) in the risk area on the day of AMI and a mean of 24 days later. RESULTS: The low reflow zone was observed shortly after PTCA in 14 verapamil group patients, and the low reflow ratio decreased after verapamil (0.39 +/- 0.23 vs. 0.29 +/- 0.17 [mean +/- SD], p < 0.05). Peak intensity significantly (p < 0.05) increased from 6 +/- 5 to 12 +/- 6 after verapamil. The reduction in wall motion score from the acute (day -1) to the late stage (day -24) was significantly greater in the verapamil group than in the control group (0.7 +/- 0.8 vs. 0.2 +/- 1.3, respectively, p < 0.05). CONCLUSIONS: Intracoronary administration of verapamil after primary PTCA can attenuate microvascular dysfunction and thereby augment myocardial blood flow in patients with AMI, leading to better functional outcome than with PTCA alone.

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.

Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction.

OBJECTIVES: We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect on microvascular function and functional and clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND: Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia. METHODS: We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41). All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography (MCE) with the intracoronary injection of sonicated microbubbles. In the nicorandil group, we injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by oral nicorandil (15 mg/day). RESULTS: The improvement in regional left ventricular function, wall motion score and regional wall motion was significantly better in the nicorandil group then in the control group. Intractable congestive heart failure, malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05, respectively). The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicorandil group than in the control group (15% vs. 33%, p < 0.05). CONCLUSIONS: Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI. Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicorandil may be attributable to this better outcome.

Doppler echocardiographic quantitation of cross-sectional area under various hemodynamic conditions: an experimental validation in a canine model of supravalvular aortic stenosis.

The hemodynamic effects on cross-sectional area calculated with the continuity equation were assessed in canine experiments. In 13 open chest dogs, 46 supravalvular aortic stenoses were created by aortic root banding. The cross-sectional area of the stenosis was calculated by Doppler echocardiography with application of the continuity equation before and after the following hemodynamic interventions: protocol 1, atrial pacing at 90, 120, 150 and 180 beats/min after sinus node crush; protocol 2, preload reduction by mild and severe clamping of the inferior vena cava; and protocol 3, afterload augmentation by mild and severe clamping of the descending aorta. In each observation, a dimension of the stenosis was directly measured by two-dimensional echocardiography, and the cross-sectional area was determined as a reference standard. As a result of the hemodynamic interventions, significant changes were observed in stroke volume and pressure gradient (protocol 1), in cardiac output, stroke volume and pressure gradient (protocol 2) and in heart rate, cardiac output and pressure gradient (protocol 3). Despite these changes in hemodynamic variables, the Doppler-derived cross-sectional area showed no significant change for a given stenosis. In addition, areas calculated with the continuity equation (x) agreed well with those determined by two-dimensional echocardiography (y) (r = 0.96, p less than 0.001, y = 0.97x + 0.02, SEE = +/- 0.06 cm2). Thus, it is concluded that Doppler echocardiography with application of the continuity equation accurately predicts the stenotic cross-sectional area over a wide range of hemodynamic conditions in supravalvular aortic stenosis.

Renin angiotensin system-dependent hypertrophy as a contributor to heart failure in hypertensive rats: different characteristics from renin angiotensin system-independent hypertrophy.

OBJECTIVES: This study aimed to characterize the difference between renin angiotensin system (RAS)-dependent and RAS-independent hypertrophy and their differential contribution to the transition to heart failure. BACKGROUND: Hypertensive left ventricular (LV) hypertrophy develops with RAS activation in the heart; however, LV hypertrophy develops even without RAS activation. METHODS: Left ventricular geometry and function were assessed in Dahl salt-sensitive rats placed on an 8% NaCl diet from seven weeks old (hypertensive rats) and in those placed on an 0.3% NaCl diet (control rats, n = 8). The hypertensive rats were randomized to no treatment (n = 8) or treatment with the angiotensin type 1 receptor (AT1R) antagonist candesartan (1 mg/kg per day, n = 10) after the baseline echocardiography study. RESULTS: From 7 to 13 weeks, AT1R blockade at a subdepressor dose did not restrain the development of LV hypertrophy but prevented narrowing of LV diastolic dimension, leading to the normalization of abnormally decreased end-systolic wall stress in the untreated rats. Progressive development of LV hypertrophy in spite of lower than normal end-systolic wall stress (excessive hypertrophy) after 13 weeks was suppressed by the AT1R blockade. Elevation of LV end-diastolic pressure and prolongation of Tau were associated with histological evidence of myocyte hypertrophy and massive interstitial fibrosis in the untreated rats, and none of these was evident in the treated rats. CONCLUSIONS: Renin-angiotensin system activation and AT1R signaling may be dispensable for the development of early adaptive LV hypertrophy and closely linked to the transition to heart failure.

Pressure-derived collateral flow index as a parameter of microvascular dysfunction in acute myocardial infarction.

OBJECTIVES: The goal of this study was to examine the implications of the pressure-derived collateral flow index (CFIp) in acute myocardial infarction (AMI). BACKGROUND: Higher CFIp is associated with less severe myocardial ischemia during angioplasty in the non-infarcted heart. It remains unknown whether CFIp also identifies collateral function in AMI patients with and without no-reflow phenomenon. METHODS: The study population included 48 patients with a first AMI. After successful percutaneous transluminal coronary angioplasty (PTCA) stent, we measured mean aortic pressure (Pa), central venous pressure (Pv) and coronary wedge pressure (Pcw) of the infarct-related artery to calculate: CFIp = (Pcw - Pv)/(Pa - Pv). Myocardial contrast echocardiography (MCE) was performed with the intracoronary injection of microbubbles to assess myocardial perfusion. Left ventriculograms at days 1 and 28 were provided for the measurement of the regional wall motion (RWM, SD/chord). RESULTS: There was no difference in CFIp among subsets based on angiographic collateral grades (grade 0, 1, 2, 3; 0.28 +/- 0.07, 0.27 +/- 0.09, 0.27 +/- 0.08, 0.23 +/- 0.08, p = NS). The CFIp was significantly higher in patients with MCE no-reflow (n = 16) than in those with MCE reflow (n = 32) (0.34 +/- 0.07 vs. 0.23 +/- 0.06, p < 0.01). There was a significant inverse correlation between the extent of functional improvement (DeltaRWM[28 d-1 d]) and CFIp (r = 0.56, p < 0.01), implying that higher CFIp is associated with worse functional improvement. CONCLUSIONS: In AMI, CFIp is unlikely to reflect collateral function but seems to increase with the severity of microvascular dysfunction. Because higher CFIp was associated with poorer functional recovery, it provides a simple and useful estimate of clinical outcomes in AMI.

Effects of atrioventricular interval on left ventricular diastolic filling assessed with pulsed Doppler echocardiography.

Effects of changes in atrioventricular interval on left ventricular diastolic filling were studied using pulsed Doppler echocardiography in 14 patients with programmable dual chamber pacemakers. Peak early diastolic filling velocity (E) and peak atrial filling velocity (A) were measured from the transmitral flow velocity pattern at three different atrioventricular intervals under the same pacing rate of 80 beats.min-1 in each patient. When the atrioventricular interval was switched from intermediate [148(SD10) ms] to short [68(11) ms], stroke volume did not change significantly [60(14) to 58(13) ml], but E increased from 39(12) to 44(11) cm.s-1 (p less than 0.05), and A decreased from 48(8) to 38(9) cm.s-1 (p less than 0.05). At the short atrioventricular interval, incomplete atrial emptying by the atrial contraction seemed to cause a reciprocal increase in the early diastolic filling. When the atrioventricular interval was switched from intermediate to long [234(16) ms], stroke volume, E and A did not change significantly [57(14) ml, 37(13) cm.s-1, 51(8) cm.s-1 respectively]. At the short and long atrioventricular intervals, atrial filling always changed in the direction opposite to that of early diastolic filling. Changes in stroke volume as well as peak early diastolic filling velocity caused by altering atrioventricular interval were pronounced in aged patients and patients with decreased early diastolic filling. In conclusion, left ventricular diastolic filling patterns can be affected by atrioventricular interval even without any concomitant pathological changes in the left atrial or ventricular function. These effects should not be taken lightly, especially in patients with decreased left ventricular early diastolic filling.