Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography.

The purpose of this study was to compare the angiotensin II type 1 receptor antagonist candesartan cilexitil (candesartan) and the angiotensin-converting enzyme inhibitor cilazapril on cardiac function, assessed by Doppler echocardiography and cardiac gene expression associated with cardiac remodeling, in rats with myocardial infarction. Candesartan or cilazapril was administered after myocardial infarction. At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA expression in noninfarcted myocardium were analyzed. Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration, measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1 week after myocardial infarction. Candesartan and cilazapril, administered at a dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks and expression of collagen I and III at 4 weeks to a similar extent. When given at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac dysfunction and gene expression to the same extent as when given at 1 mg/kg per day. In conclusion, Doppler echocardiography showed that candesartan and cilazapril equally improved systolic and diastolic function and that ventricular remodeling accompanied modulation of cardiac gene expression.

Effects of preinfarction angina on myocardial injury in patients with acute myocardial infarction: a study with resting 123I-BMIPP and 201T1 myocardial SPECT.

METHODS: Recent studies have suggested that patients with preinfarction angina have smaller infarcts and a better in-hospital outcome than those without angina. The mechanisms responsible for limitation of infarct size in the presence of preinfarction angina are unclear. We examined the effects of preinfarction angina on myocardial injury in patients with the first acute myocardial infarction with resting 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) 201TI myocardial scanning performed within 1 mo of infarction. RESULTS: Of 136 patients tested, 48 (35%) had preinfarction angina within 72 h before infarction, whereas 88 (65%) did not. BMIPP and 201TI defects were scored in 9 segments of the left ventricle (0 = normal, 1 = mild defect, 2 = moderate defect, 3 = severe defect, and 4 = no uptake). The total defect score was defined as the sum of the defect scores. There was no significant difference in percentage diameters of stenoses of infarct-related arteries, collateral circulation, total defect scores for BMIPP, or 201TI between the groups with and without preinfarction angina. However, the ratio of total defect score for 201TI to that for BMIPP was significantly smaller for patients with than for those without preinfarction angina (0.64 +/- 0.21 versus 0.74 +/- 0.25, respectively; P = 0.007). CONCLUSION: Preinfarction angina did not affect the areas at risk in acute myocardial infarction, as shown by BMIPP defect, but decreased necrotic myocardium in the areas at risk, as shown by 201TI defect, and increased metabolically damaged but viable myocardium, as shown by BMIPP and 201TI mismatch through unidentified mechanisms other than collateral circulation (e.g., ischemic preconditioning).

Circulating immunoreactive endothelin in patients undergoing percutaneous transluminal coronary angioplasty.

Circulating immunoreactive endothelin (ir-ET) in the coronary sinus (CS) and the femoral artery (Ao) was measured in patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Plasma ir-ET level in the CS was significantly increased from 1.6 +/- 0.8 pg/mL to 2.0 +/- 1.0 pg/mL after PTCA (P less than .05). Plasma ir-ET level in the Ao tended to increase after PTCA, but it was not significant. Plasma ir-ET level in the CS was not related to the plasma thromboglobulin level, plasma thrombin-antithrombin complex level, mean blood pressure, or heart rate. These results suggest that the increase of plasma ir-ET level in the CS may be associated with the coronary endothelial injury by PTCA.

Potential applications of intracardiac echocardiography in the assessment of the aortic valve from the right ventricular outflow tract.

Intracardiac echocardiography (ICE) is a developing technology and a promising method for visualizing intracardiac structures. However, its applications are currently limited to guidance during mitral valvuloplasty, catheter ablation, or electrophysiologic examination. The goal of this study was to observe the aortic valve, measure the annular diameter of the valve by ICE through a right-sided approach, and compare the results by ICE with those by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE). We studied 18 patients (9 men, 9 women, aged 19 to 72 years) with various heart diseases, including 15 patients with mitral or aortic valvular disease. An imaging catheter was advanced through a long sheath into the outflow tract of the right ventricle. We obtained good longitudinal views of the aortic valve in all patients. Two of the 18 patients had poor image quality by TTE. The annular diameter by ICE correlated more closely with TEE than with TTE. In conclusion, right-sided ICE is a safe, simple, and useful procedure for observing the aortic valve during cardiac catheterization without additional discomfort in the patients. Right-sided ICE is superior to TTE in observing the aortic valve and measuring the annular diameter of the valve. The annular diameter can be measured by ICE as precisely as by TEE.

Assessment of transmural coronary blood flow with intraoperative transesophageal color Doppler echocardiography during coronary revascularization.

Intraoperative color Doppler transesophageal echocardiography with a 4- to 7-MHz transducer was performed on 28 consecutive patients who underwent coronary artery bypass grafting to image and evaluate the transmural coronary blood flow before and after cardiopulmonary bypass. The transmural coronary flow was visualized in 26 (92.8%) of 28 patients in the inferior wall and in 13 (46.4%) of 28 patients in the lateral wall. The peak diastolic flow velocity of the transmural coronary artery in the inferior and lateral wall was significantly increased after coronary revascularization in patients with a successful bypass graft to the right coronary artery (from 34.0 +/- 19.7 to 64.9 +/- 30.9 cm/s, P <.001, n = 10) and to the left circumflex coronary artery (from 35.1 +/- 18.6 to 62.1 +/- 21.1 cm/s, P <.001, n = 10). No significant changes were observed in patients with no bypass graft to the right or left circumflex coronary artery. Coronary blood flow can be mapped and the velocity measured with Doppler transesophageal echocardiography with a high-frequency (4- to 7-MHz) transducer. Assessment of the transmural coronary flow may provide valuable information and aid in decision making during surgical revascularization.

Assessment of membrane protection by 31P-NMR effects of lidocaine on calcium-paradox in myocardium.

In studying calcium paradox, perfused rat hearts were used to investigate the myocardial protective effects of lidocaine. Intracellular contents of phosphates were measured using the 31P-NMR method. In hearts reexposed to calcium, following 3 minute calcium-free perfusion, a rapid contracture occurred, followed by rapid and complete disappearance of intracellular phosphates with no resumption of cardiac function. In hearts where lidocaine was administered from the onset of the calcium-free perfusion until 2 minutes following the onset of reexposure to calcium, both intracellular phosphates and cardiac contractility were maintained. Therefore, it can be said that cell membranes were protected by lidocaine.

Hereditary hemorrhagic telangiectasia with growing pulmonary arteriovenous fistulas followed for 24 years.

A 47-year-old man was admitted for follow-up of an abnormal chest x-ray. He had a history of epistaxis and a brain abscess and a family history of pulmonary arteriovenous fistulas. Physical examination showed clubbed fingers and telangiectasia of the tongue. Laboratory data revealed evidence of polycythemia and hypoxia. Contrast echocardiography and pulmonary perfusion scintigraphy were suggestive of a right-to-left shunt. From the oxygen tension and content of blood taken at cardiac catheterization, the shunt ratio was calculated to be 57.8%. Multiple bilateral pulmonary arteriovenous fistulas were confirmed by angiography, and the patient was diagnosed as having hereditary hemorrhagic telangiectasia. A review of x-ray films taken over a 24-year period demonstrated that the fistulas in both lungs had been increasing gradually in size at different rates. A right lower lobectomy relieved the hypoxia, but the patient died unexpectedly on the twelfth postoperative day. There was no evidence of fistula rupture on chest film, but no autopsy was performed.

Pheochromocytoma with electrocardiographic change mimicking angina pectoris, and cyclic change in direct arterial pressure--a case report.

A forty-two-year-old man was admitted because of chest pain. Electrocardiograms at admission showed horizontal ST depression in leads, II, III, aVF, V4, V5, and V6. Direct blood pressure monitoring revealed cyclic change between 160/100 mmHg and 70/50 mmHg and heart rate between 80/sec and 120/sec at fifteen minute intervals. The plasma norepinephrine and epinephrine concentrations were elevated during the episodes of hypertension. Pheochromocytoma was found in the right adrenal gland. These cyclic changes in blood pressure and heart rate are an aid for diagnosis.

[Malignant thymoma detected by thallium-201 myocardial scintigraphy].

We present two cases of malignant thymoma which showed a remarkable accumulation of thallium-201 chloride on myocardial scintigraphy. A 69 year-old man underwent stress 201Tl scintigraphy to evaluate myocardial ischemia and abnormal accumulation of thallium activity was observed in the anterior mediastinum by chance. It was more clearly visualized on delayed image. Moreover, abnormal uptake of 67Ga citrate was also observed in the same region. In another 68 year-old woman, there was high uptake on 201Tl scintigraphy, but no abnormal uptake using 67Ga. The diagnosis of malignant thymoma was confirmed by operation in each patient. These two cases had no abnormality in the mediastinum on the chest X-ray film and one of them had no uptake of 67Ga, 201Tl scintigraphy was more useful to detect malignant thymoma.

[Clinical usefulness of intracoronary Doppler for prediction of coronary restenosis].

The Doppler guide wire is widely used in the diagnosis of heart diseases, and in particular including ischemic heart disease. It offers various advantages for application in tortuous and peripheral arteries, and in the detection of functional coronary stenosis that coronary angiography cannot detect. A number of multicenter trials have also shown that the Doppler guide wire is of value in predicting coronary restenosis after coronary intervention. On the other hand, the Doppler guide wire is influenced not only by the stenosis in the epicardial coronary artery, but also by stenosis in the vascular beds of coronary microcirculation. An appreciation of both the advantages and disadvantages of the Doppler guide wire and its usefulness is of considerable importance.

Circulating atrial natriuretic polypeptide during exercise in patients with essential hypertension.

We studied the relationship between haemodynamic measurements and plasma atrial natriuretic peptide (ANP) levels during exercise in patients with essential hypertension. The exercise protocol consisted of three fixed work loads (25, 50 and 75 W) using a supine bicycle ergometer. Plasma ANP levels and haemodynamic indices were measured before and during each stage of exercise. Plasma ANP levels and pulmonary artery wedge pressure (PAWP) significantly increased at the maximum work load. Significant correlations of PAWP and mean arterial pressure (MAP) to plasma ANP levels were observed at four points obtained before and during each stage of exercise (PAWP, r = 0.83, P less than 0.001; MAP, r = 0.48, P less than 0.01). Furthermore, a significant inverse correlation between shortening fraction (SF), estimated by M-mode echocardiography, and plasma ANP levels at 75 W work load was also observed (r = -0.66, P less than 0.01). These results suggest that the increase of circulating ANP levels during exercise in essential hypertensive subjects may be associated with elevated left atrial pressure and arterial pressure, or left ventricular systolic dysfunction.

Clinical and histologic features of alcohol drinkers with congestive heart failure.

To clarify the difference between alcoholic cardiomyopathy and dilated cardiomyopathy and to investigate the characteristics of alcoholic cardiomyopathy, right ventricular endomyocardial biopsy was performed, and the two diseases were compared clinically and histologically. Changes in the cardiothoracic ratio, cardiac index, and systolic blood pressure/end-systolic volume index were greater after treatment in patients with alcoholic cardiomyopathy than in patients with dilated cardiomyopathy. Histologically, myocytic hypertrophy, fibrosis, and nuclear change were less significant in the former than in the latter. Among patients with alcoholic cardiomyopathy, the cardiac index in those with less fibrosis was greater than in those with more fibrosis. Thus patients with alcoholic cardiomyopathy had more preserved and reversible cardiac function and fewer histologic changes than the patients with dilated cardiomyopathy. Reversibility of cardiac function in patients with alcoholic cardiomyopathy correlated inversely with the severity of histologic changes.

Histopathological study on the effects of aging in myocardium of hypertrophied hearts.

To clarify the effects of aging in myocardium of hypertrophied hearts, 555 autopsied hearts were studied histopathologically. Degrees of myocyte hypertrophy, disarrangement and fibrosis and lipofuscin deposits were estimated light-microscopically in tissue specimens taken from the anterior wall of the left ventricle. Myocyte hypertrophy was assigned to one of four classes from 0 to 3+ according to size. Other findings were estimated using the conventional three classes. All cases were divided according to heart weight, into the following groups: severe hypertrophy (Group I; more than 450 g for males and 400 g for females), mild hypertrophy (Group II; 450 greater than HW greater than 350 g for males and 400 greater than HW greater than 300 g for females) and no hypertrophy (Group III: less than 350 g for males and 300 g for females). Lipofuscin deposits increased with aging, but in Group I the increase was delayed in comparison to that in other groups. As a rule, myocyte size in the outer layer was equal to or smaller than that in the inner layer (outer-layer-selective atrophy). This was particularly true in pressure-overloaded hypertrophy and less so in volume-overloaded hypertrophy. Myocyte disarrangement was observed in the inner and median layers in the oldest group. Peri-vascular fibrosis became thick with aging, and perimysial fibrosis increased with age. The fibrotic process was accelerated in hypertrophied myocardium. As to the mode of hypertrophy, aging appears to result in a kind of myocardial asymmetry of layer-selective atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Point mutations in mitochondrial DNA of patients with alcoholic cardiomyopathy.

The pathogenesis of alcoholic cardiomyopathy (ACM) is not well understood. However, recent reports have shown that mutations in mitochondrial DNA (mtDNA) were associated with mitochondrial encephalomyopathy and cardiomyopathy. Our objective was to explore point mutations in mtDNA and the pathogenesis of ACM. We obtained heart biopsy specimens from ten male habitual drinkers with congestive heart failure. We amplified the total mtDNA obtained from these specimens using a two-step polymerase chain reaction method and analyzed the products using automated fluorescence-based direct sequencing. The sequences were compared with those of controls. MtDNA from the ACM patients contained multiple point mutations. Specifically, four of the ten patients carried five point mutations that had been detected previously in several other mitochondrial diseases. These point mutations were not observed in controls. These results suggest that mtDNA abnormalities are involved in the pathogenesis of ACM.

Prediction of contractile reserve by cyclic variation of integrated backscatter of the myocardium in patients with chronic left ventricular dysfunction.

OBJECTIVE: To clarify whether assessment of the acoustic properties of the myocardium at rest can predict contractile reserve in patients with chronic left ventricular dysfunction. METHODS: 23 patients (mean (SD) age 63 (12) years) with chronic left ventricular dysfunction were studied. The magnitude of cardiac cycle dependent variation of integrated backscatter (CVIB) of the myocardium was measured at rest in the basal and mid segment of the septum and posterior wall of the left ventricle, using a real time two dimensional integrated backscatter imaging system. The results were compared with the percentage wall thickening and the wall motion at rest and during low dose dobutamine infusion. The wall motion was graded as normal, hypokinetic, or akinetic and contractile reserve was considered present when an akinetic or hypokinetic segment improved during dobutamine infusion. RESULTS: The CVIB at rest correlated with per cent wall thickening at rest and during dobutamine infusion (at rest, r = 0.61, p < 0.0001, during dobutamine, r = 0.76, p < 0.0001). Of the 76 segments examined, 27 showed contractile reserve. The mean CVIB at rest was significantly greater in segments with contractile reserve than in those without (p < 0.0001). CVIB above 3 dB at rest predicted segments with contractile reserve with a sensitivity and specificity of 81% and 60%, respectively (p < 0.0001). CONCLUSIONS: CVIB reflected not only myocardial contractility but also the functional capacity of the myocardium. It predicted segmental contractile reserve in patients with chronic left ventricular dysfunction.

Real time quantification of low temperature radiofrequency ablation lesion size using phased array intracardiac echocardiography in the canine model: comparison of two dimensional images with pathological lesion characteristics.

OBJECTIVE: To evaluate the feasibility of quantifying low temperature radiofrequency catheter ablation (RFCA) lesions using a phased array intracardiac echocardiography (ICE) catheter--with better tissue penetration and in a deflectable device-in the canine model. INTERVENTION: Low temperature radiofrequency (RF) energy (50-60 degrees C at up to 40 W) was delivered to the left ventricle in 11 beagles for 60 seconds, using an 8 French catheter with a deflectable tip and a 4 mm distal electrode. MAIN OUTCOME MEASURES: Comparison of the width and depth of RFCA lesions measured by ICE with pathological findings. RESULTS: 33 RF energies were delivered in 11 dogs. 31 lesions (94%) were confirmed at necropsy. 27 of 31 ablation lesions (87%) were detected by ICE. The mean (SD) width and depth of the ICE detected lesions were 10.4 (2.6) mm and 5.7 (1.9) mm, respectively. Pathological findings showed that RFCA lesions consisted of inner and outer layers. Macroscopically, the mean (SD) width and depth of the inner layers were 7.6 (2.3) mm and 3.6 (1.2) mm and those for the whole layers were 10.0 (2.8) mm and 5.3 (1.5) mm, respectively. Microscopically, the inner and outer layers corresponded to necrotic and oedematous areas, respectively. The ICE detected lesion size had better correlation with the pathological measurements of the whole layers in width (r = 0.911) and in depth (r = 0.756). CONCLUSION: The real time evaluation of RFCA lesion size using the phased array ICE is feasible, even with a low temperature RF application. However, ICE slightly overestimates RFCA lesion size compared with pathological necrotic lesion size.