Hisayoshi Fujiwara

Ventricular expression of brain natriuretic peptide in hypertrophic cardiomyopathy.

BackgroundBrain natriuretic peptide (BNP), as a cardiac hormone, is expressed together with atrial natriuretic peptide (ANP) in the ventricles in congestive heart failure. However, the ventricular expression of BNP in hypertrophic cardiomyopathy (HCM) with normal systolic function is still unclear. Methods and ResultsThe study population consisted of 39 HCM patients with asymmetric septal hypertrophy and 10 control subjects without any specific cardiac disease. Eleven cases of HCM were obstructive (HOCM), and the other 28 cases were nonobstructive (HNCM). All of these patients had a normal ejection fraction. Immunohistochemical analysis of endomyocardial biopsy specimens with specific monoclonal antibodies showed BNP immunoreactivity in the HOCM group (5/10, 50%) but not in the HNCM group (0/22) or in control subjects (0/5). In HOCM, left ventricular end-diastolic pressure was significantly higher in the BNP-positive patients than the BNP-negative patients. Histological changes such as myocardial fiber disarray, hypertrophy of myocytes, and fibrosis were greater in BNP-positive patients than BNP-negative patients in HCM. However, the expression had no significant relation with other clinical parameters. The elevation of the BNP plasma level versus control subjects was marked in both HOCM (85-fold) and HNCM (23-fold). By contrast, the elevation of the ANP plasma level versus control subjects was mild in HOCM (5.7-fold) and HNCM (4.2-fold). The ratio of BNP level to ANP level was higher in HOCM (4.16) than in HNCM (1.46) and control subjects (0.28), and it was higher than the ratio previously reported for severe congestive heart failure (1.72). ConclusionThese findings suggest that BNP is expressed in the ventricular myocytes of HCM with normal systolic function. In HOCM, ventricular expression of BNP may be augmented in response to both obstruction and diastolic dysfunction.

Ischemic preconditioning preserves creatine phosphate and intracellular pH.

BackgroundIschemic preconditioning slows ATP depletion and ultrastructural damage during the final episode of ischemia. To define the influence of creatine phosphate (CP) and intracellular pH (pHi) on this effect, CP and pHi were serially measured in porcine hearts without collateral circulation by using 31P-NMR spectroscopy and ultrastructural examination. Methods and ResultsFarm pigs weighing 12–15 kg were anesthetized with Fluothane. The control group underwent a single occlusion (20 minutes or 60 minutes); the preconditioned group underwent four episodes of 5-minute occlusion and 5-minute reperfusion followed by a sustained occlusion (20 minutes or 60 minutes). After ischemic preconditioning, CP increased to 115 ± 11% (p < 0.05) of preischemic value and ATP decreased to 84 ± 8% (p < 0.05) of preischemic value, but pH; returned to preischemic value. At 5 and 10 minutes of sustained ischemia, CP was significantly preserved in the preconditioned group (control group, 19 ± 3% versus preconditioned group, 29 ± 4% at 5 minutes; control group, 5 ± 3% versus preconditioned group, 11 ± 3% at 10 minutes; p < 0.05). At 15 and 20 minutes of sustained ischemia, ATP was significantly preserved in the preconditioned group (control group, 64 ± 3% versus preconditioned group, 73 ± 3% at 15 minutes; control group, 51 ± 7% versus preconditioned group, 62 2% at 20 minutes; p < 0.05). At 10, 15, 20, and 25 minutes of sustained ischemia, pH; was significantly higher in the preconditioned group (control group, 6.5 0.05 versus preconditioned group, 6.7 ± 0.1 at 10 minutes; control group, 6.3 0.05 versus preconditioned group, 6.6 0.06 at 15 minutes; control group, 6.1 ± 0.1 versus preconditioned group, 6.4 % 0.1 at 20 minutes; control group, 6.0 0.2 versus preconditioned group, 6.3 ± 0.1 at 25 minutes; p < 0.05). Ultrastructural changes were milder in the preconditioned group at 20 minutes of sustained ischemia. ConclusionsIn addition to ATP and ultrastructure, preconditioning preserved CP and pHi during sustained ischemia. These protective effects might be due to overshoot phenomenon of CP and/or reduced ATP consumption. The relatively longer period of preservation of pH;, which probably is the result of reduced ATP consumption, indicates its greater contribution to reducing infarct size than that of CP and ATP.

Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.

To elucidate the expression of the atrial natriuretic polypeptide (ANP) gene in the ventricle of the human failing heart, we have measured ANP and ANP messenger RNA (ANPmRNA) levels in left ventricular aneurysm obtained at operation, biopsy specimens of left ventricles from dilated cardiomyopathy (DCM) and autopsy samples of old myocardial infarction (OMI) and DCM hearts, and compared the levels with those in the normal ventricle. The ANP level (mean +/- SE) was 17.5 +/- 6.9 ng/g in the normal ventricle, and increased to 660.3 +/- 122.2 ng/g in the left ventricular aneurysm tissues and to 3,138.6 +/- 1,642.1 ng/g in the biopsy specimens of the DCM ventricle. These levels were approximately 40 and 200 times higher than in the normal ventricle. The increase of ANP levels was observed in both infarcted and noninfarcted regions of the OMI heart, and in the entire ventricle of the DCM heart. A significant positive correlation was found between the ANP level in aneurysm tissues and pulmonary capillary wedge pressure (r = 0.85). The ANPmRNA level in the left ventricular aneurysm showed about a 10-fold increase compared with that in the normal heart and reached 23% of that in the atrium of the same heart. A similar increase in the ANPmRNA level was observed in the entire ventricle of DCM. These data clearly indicate that the expression of the ANP gene in the ventricle is augmented in the failing heart in accordance with the severity of heart failure. In the atrium of the failing heart, ANP and ANPmRNA levels were only two times higher than those in the normal atrium. Thus, the augmentation in the expression of the ANP gene was more prominent in the ventricle than in the atrium. Taking tissue weight into account, the total content of ANPmRNA in the ventricle of the failing heart is much the same as that in the normal atrium. The ratio of the ANP level to the ANPmRNA level in the ventricle is much smaller than that in the atrium. These results suggest more rapid secretion of ANP after synthesis in the ventricle. These findings demonstrate that the expression of the ANP gene is augmented in the human ventricle of the failing heart and suggest that the ventricle becomes a substantial source of circulating ANP in congestive heart failure.

Histologic studies in percutaneous transluminal coronary angioplasty for chronic total occlusion: Comparison of tapering and abrupt types of occlusion and short and long occluded segments

OBJECTIVES The purpose of this study was to examine the histologic-angiographic correlates of chronic total coronary occlusion and to explain why a tapering type of occlusion and short occluded segments are favorable for percutaneous transluminal coronary angioplasty. BACKGROUND Coronary angioplasty is less successful for vessels with chronic total occlusion than for highly stenotic but patent vessels. Several clinical and angiographic factors determining the rate of initial success have been investigated, but the underlying histologic features are not clear. METHODS Ten autopsy hearts that showed chronic total coronary occlusion on cineangiography performed < or = 3 months before death were selected. In all, the estimated duration of occlusion was > 1 year. At autopsy, postmortem angiography was performed and hearts were fixed with 10% buffered formalin. Occluded segments were sectioned transversely and serially into slices 10 microns thick. Every five slices were stained in hematoxylin-eosin and elastic van-Gieson. RESULTS Ten hearts with chronic total coronary occlusion were angiographically classified into five with a tapering and five with an abrupt type of occlusion and seven with a short (< or = 15 mm) and three with a long (> 15 mm) occluded segment. Histologically, the occluded segment was composed of loose or dense fibrous tissue, atheroma, small vascular channels and calcified tissue. Reconstruction of the serial preparations showed that small lumen recanalized areas (diameter 160 to 230 microns) with surrounding loose fibrous tissue penetrated the occluded segment in four hearts with occlusion of the tapering type and a short occluded segment. In these four cases, the lack of anterograde flow on cineangiography could be explained by the presence of rich collateral flow. In three cases of the abrupt type of occlusion with a short occluded segment, a mass of loose fibrous tissue penetrated the occluded segment. In hearts with a long occluded segment (one with a tapering type of occlusion and two with an abrupt type), there was no recanalization and loose fibrous tissue was dispersed in the occluded segment. CONCLUSIONS Chronic total coronary occlusion of the tapering type or with a short occluded segment, or both, is possibly favorable for angioplasty, because small lumen recanalized areas or loose fibrous tissue penetrates the occluded segment and may form a route for successful angioplasty.

Role of the left atrium in adaptation of the heart to chronic mitral regurgitation in conscious dogs.

The manner in which the left atrium adapts to chronic mitral regurgitation and the role of the adapted left atrium as a modulator of excessive central blood volume were analyzed in seven conscious dogs, instrumented with high-fidelity pressure transducers and ultrasonic dimension gauges for measurement of left atrial and left ventricular pressure and cavity size. After obtaining data in a control situation, mitral regurgitation was produced by transventricular chordal sectioning. Heart rate was matched by right atrial pacing. In the “early” stage (7–14 days), left ventricular end-diastolic and mean left atrial pressures increased from 6 to 16 mm Hg and from 4 to 12 mm Kg, respectively. Both left ventricular end-diastolic segment length and left atrial diameter prior to atrial contraction increased by 7%. In the “late” stage (20–35 days), despite significant decreases in left ventricular filling pressure (11 mm Hg) and left atrial pressure (8 mm Hg), there was a continuous increase in left ventricular end-diastolic dimension (10%) and atrial end-diastolic diameter (10%). After the onset of mitral regurgitation, the left atrium performed greater work with a more enlarged cavity. Left atrial chamber stiffness was progressively decreased. These changes were associated with progressive increase in the left atrial diameter at zero stress, and there was a significant increase in the diameter of the left atrial myocyte. These results indicate that during chronic mitral regurgitation, the left atrium enlarges in size and mass, with a more potent booster action. The left atrial chamber becomes more compliant. Thus, the enlarged left atrium appears to exert an important compensatory mechanism in the case of excessive central blood volume by buffering pressure rise in the atrium and by providing an adequate ventricular filling volume.

Preconditioning improves energy metabolism during reperfusion but does not attenuate myocardial stunning in porcine hearts.

BackgroundIt has been reported that a brief period of coronary occlusion and reperfusion slows the rate of ATP depletion during subsequent sustained ischemia as well as limiting infarct size. However, it has not yet been determined whether ischemic preconditioning also has an effect on the functional and metabolic recovery of stunned myocardium. Our study was designed to address this problem. Methods and ResultsFarm pigs were anesthetized with fluothane and randomly assigned to either a control group or a preconditioned group. The control group (n=15) underwent 15 minutes of coronary occlusion followed by 120 minutes of reperfusion. The preconditioned group (n=14) underwent two episodes of 5-minute occlusion and 5-minute reperfusion followed by 15 minutes of occlusion and 120 minutes of reperfusion. This protocol was designed to exclude the stunning effect of the preconditioning procedure itself as much as possible besides preconditioning the heart. A pair of ultrasonic crystals was implanted in the area at risk perfused by the left anterior descending coronary artery. 31P-nuclear magnetic resonance spectroscopy and sonomicrometry were performed alternately. Regional myocardial blood flow (RMBF) was determined with colored microspheres. At 15 minutes of sustained ischemia, phosphocreatine (Pcr), ATP, and intracellular pH were significantly better preserved in the preconditioned group (Pcr: control/preconditioned, 1±1%/o/14

Expression and distribution of atrial natriuretic peptide in human hypertrophic ventricle of hypertensive hearts and hearts with hypertrophic cardiomyopathy.

1%; ATP:control/preconditioned, 66

Light and electron microscopic localization of brain natriuretic peptide in relation to atrial natriuretic peptide in porcine atrium. Immunohistocytochemical study using specific monoclonal antibodies.

2%1/74

Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts. Immunohistochemical study of the endomyocardial biopsy specimens.

2%; pH:control/preconditioned, 632

Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis.

0.07/6.52