[Clinical significance of plasma atrial and brain natriuretic peptide levels during hemodialysis in hemodialysis patients with old myocardial infarction].

OBJECTIVES: The plasma levels of atrial natriuretic peptide(ANP) and brain natriuretic peptide(BNP) are useful to evaluate left ventricular function in patients with old myocardial infarction(OMI). This echocardiographic study examined the clinical importance of the measurement of ANP and BNP in patients with OMI undergoing hemodialysis. METHODS: ANP and BNP levels were measured before and after hemodialysis in 36 patients with OMI and 42 patients without ischemic heart disease as controls(control group). Echocardiography was performed after hemodialysis. The patients with OMI were classified into two groups according to left ventricular percentage fractional shortening(% FS): Normal(OMI-N) group with %FS > or = 30%(n = 19) and low (OMI-L) group with %FS < 30%(n = 17). RESULTS: The ANP, BNP levels and BNP/ANP ratio before and after hemodialysis were significantly higher in the OMI-L group than in the other groups. BNP level was significantly inversely correlated with %FS(r = -0.60, p < 0.05) and correlated with E wave and E/A, in mitral inflow only in the OMI-L group. The decrease in BNP level during hemodialysis was significantly greater in the OMI-L group than in the other groups, but not in ANP level. CONCLUSIONS: These findings suggest that ANP and BNP levels are increased in patients with left ventricular dysfunction undergoing hemodialysis compared to those with normal left ventricular function. ANP level is convenient for decision of suitable dry weight. In contrast, BNP level that correlated inversely with impairment of left ventricular function is a more sensitive index of left ventricular function than ANP in patients with OMI undergoing hemodialysis.

Nicorandil enhances cardiac endothelial nitric oxide synthase expression via activation of adenosine triphosphate-sensitive K channel in rat.

In the heart, nitric oxide activates an adenosine triphosphate (ATP)-sensitive K (K(ATP)) channel that is constructed of two subunits, i.e., an ATP-binding cassette protein sulfonylurea receptor (SUR2) and a pore-forming inward rectifier (Kir6.1 or 6.2). However, whether this K(ATP) channel affects nitric oxide activation is unknown. Our aim was to assess whether pharmacologic activation of the K(ATP) channel by nicorandil contributes to endothelial nitric oxide synthase (eNOS) levels. A total of 21 7-week old male Sprague-Dawley rats were used. Seven were treated by intraperitoneal injection of nicorandil at 3 mg/kg/d; seven were treated with intraperitoneal nicorandil at 3 mg/kg/d after glibenclamide at 12 mg/kg/d twice a day p.o.; and seven were left untreated (controls). At 24 h after treatment, blood pressure and heart rate were measured, and eNOS, SUR2, Kir6.1, and Kir6.2 mRNA levels and eNOS protein levels in the left ventricle were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Nicorandil caused tachycardia without a change in blood pressure, whereas glibenclamide had no effect on the nicorandil-induced change in heart rate or on blood pressure. RT-PCR revealed that nicorandil increased the eNOS and SUR2 mRNA levels by 2.2- and 2.0-fold, respectively, (p < 0.01 versus control), and that these increases were completely inhibited by glibenclamide. A significant correlation was observed between eNOS and SUR2 mRNA levels in all experimental rats (r = 0.760, p < 0.001). However, Kir6.1 or 6.2 mRNA level was constant. Western blot analysis revealed that nicorandil caused a 1.6-fold increase in eNOS protein levels (p < 0.01 versus control). This increase was completely inhibited by glibenclamide. In conclusion, up-regulation of eNOS mRNA and protein levels by nicorandil, and inhibition of this upregulation by glibenclamide, were demonstrated in normotensive conscious rat hearts. Nicorandil appears to enhance cardiac eNOS expression via activation of a K(ATP) channel.

Effects of TCV-116 on expression of NOS and adrenomedullin in failing heart of Dahl salt-sensitive rats.

We examined the effects of TCV-116, an angiotensin II type 1 receptor antagonist, on endothelial-cell nitric oxide synthase (eNOS), inducible NOS (iNOS), and adrenomedullin (ADM) expression in the left ventricle (LV) and evaluated these relation to myocardial remodeling in failing heart of Dahl salt-sensitive hypertensive rats (DS) fed a high-salt diet. TCV-116 (DSHF-T, 5 mg/kg/day, subdepressor dose) or vehicle (DSHF-V) were given from left ventricular hypertrophy to heart failure stage for 7 weeks. Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSHF-V was significantly ameliorated in DSHF-T. The eNOS mRNA and protein in the LV was significantly suppressed in DSHF-V compared with control rats (DR-C), and significantly increased in DSHF-T compared with DSHF-V. The iNOS mRNA and protein, ADM mRNA and immunoreactive ADM contents, and type I collagen mRNA in the LV were significantly increased in DSHF-V compared with DR-C, and significantly decreased in DSHF-T compared with DSHF-V. DSHF-V showed a significant increase of the wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis, with all these parameters being significantly improved by TCV-116. In conclusion, myocardial remodeling and heart failure in DS rats fed a high-salt diet were significantly ameliorated by a subdepressor dose of TCV-116, which may be due to a increased in eNOS and a decreased in iNOS mRNA and protein expression in the LV. Moreover, the ADM mRNA and immunoreactive ADM contents are upregulated in failing heart of DS rats fed a high-salt diet, and increased ADM expression may have a role in the defense mechanism against further cardiac dysfunction and impaired myocardial remodeling.

Plasma brain natriuretic peptide levels in chronic hemodialysis patients: influence of coronary artery disease.

A noninvasive biochemical testing method for early detection and monitoring the condition of cardiac complications in hemodialysis (HD) patients would be useful and might lead to improved survival. The aim of this study is to clarify the pathophysiological significance of plasma brain natriuretic peptide (BNP) levels in HD patients with and without coronary artery disease (CAD). We measured plasma atrial natriuretic peptide (ANP) and BNP levels on Monday, Wednesday, and Friday before and after HD in 28 consecutive patients who underwent HD three times weekly. In addition, we measured plasma ANP and BNP levels in 21 HD patients with CAD and 27 HD patients without CAD and studied the relationships between BNP levels and cardiac function and clinical variables. Plasma ANP levels significantly decreased after HD on Monday, Wednesday, and Friday, and predialysis plasma ANP levels on Monday were significantly greater than those on other days. Plasma BNP levels did not change after HD on Monday; however, they significantly decreased after HD on Wednesday and FRIDAY: Predialysis plasma BNP levels on Monday were greater than those on other days, and postdialysis plasma BNP levels on Monday were greater than predialysis plasma BNP levels on WEDNESDAY: Plasma BNP levels in HD patients with CAD were significantly greater than those in HD patients without CAD and significantly correlated with left ventricular (LV) ejection fraction (r = -0.69), end-diastolic volume index (r = 0.59), and end-systolic volume index (r = 0.84) determined by left ventriculography. Conversely, plasma BNP levels in HD patients without CAD significantly correlated with LV mass index (r = 0.54) determined by echocardiography and mean systolic blood pressure (r = 0.72) determined by 48-hour ambulatory blood pressure monitoring. These results suggest the following: (1) plasma BNP levels before and after HD in chronic HD patients directly correlate with the degree of body fluid retention, and the day of the week on which the sample is obtained should be considered for its evaluation; (2) plasma BNP levels reflect LV function in HD patients with CAD; and (3) plasma BNP levels reflect LV mass and blood pressure in HD patients without CAD.

Alternans of ventricular gradient during percutaneous transluminal coronary angioplasty.

We evaluated the influence of local myocardial ischemia induced by acute coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA) on the ventricular gradients (VG) and investigated whether 2:1 alternans of VG occurs. Twenty-seven patients with angina pectoris, who had one-vessel coronary artery stenosis, were studied. The VG of each consecutive heartbeat before, during, and after PTCA over a 22-second interval was calculated using a microcomputer. The standard deviation and coefficient of variation of magnitude were used as indices of VG variability. Frequency-domain analysis of time series consisting of beat-to-beat VG magnitude for a 22-second interval was also performed by the maximum entropy method. The standard deviation and coefficient of variation of VG magnitude during PTCA were significantly greater than those before and after PTCA (P <.01, P <.01, respectively), and the indices before PTCA were also significantly greater than those after PTCA (P <.05). The maximum power spectrum peaks around 0.5 cycles/beat during PTCA were significantly greater than those after PTCA (P <.01); this suggests that the enhancement of VG alternans is reflected by 2:1 alternans of the action potential in the acute local ischemic myocardium during PTCA.

Elevation of two molecular forms of adrenomedullin in plasma and urine in patients with acute myocardial infarction treated with early coronary angioplasty.

Adrenomedullin (AM) has vasodilatory, diuretic and natriuretic actions. Two molecular forms of AM circulate in human plasma: an active, mature form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly). In the present study we investigated the pathophysiological significance of the two molecular forms of AM in plasma and urine in patients with acute myocardial infarction. We serially measured venous and arterial plasma levels and urinary excretion of AM-m, AM-Gly and total AM (Am-T; =AM-m+AM-Gly) over 2 weeks using our recently developed immunoradiometric assay in 26 consecutive patients with acute myocardial infarction and in age-matched normal controls, and studied the relationships between AM levels and clinical parameters. Plasma AM-m, AM-Gly and AM-T levels were increased on admission in patients with acute myocardial infarction compared with age-matched normal controls. Levels of AM-m, AM-Gly and AM-T in plasma reached a peak 24 h after the onset of symptoms. Plasma AM-m, AM-Gly and AM-T levels were significantly correlated with plasma levels of brain natriuretic peptide and pulmonary arterial pressure. Plasma AM-Gly levels in the vein were similar to those in the artery, whereas plasma AM-m levels were significantly lower in the artery than in the vein. Urinary excretion of AM-m, AM-Gly and AM-T was also increased on admission, and reached a peak at 12 h after the onset of symptoms. Urinary excretion of AM-m and AM-Gly was significantly correlated with urinary sodium excretion. The AM-m/AM-T ratio was significantly higher in the urine than in the vein or artery. AM-m levels were significantly correlated with AM-Gly levels in both the urine and plasma; however, there were no significant correlations between plasma and urinary AM levels. The results suggest that levels of both molecular forms of AM are increased in the urine as well as in the plasma in the acute phase of myocardial infarction. Since AM exerts potent cardiovascular and renal effects, increased concentrations of AM in plasma and urine in the acute phase of myocardial infarction may be involved in the defence mechanism against further elevations of peripheral and pulmonary vascular resistance and oliguria in acute myocardial infarction.

[Mid-ventricular obstructive hypertrophic cardiomyopathy associated with an apical aneurysm and sustained ventricular tachycardia: a case report].

A 60-year-old woman presented with mid-ventricular obstructive hypertrophic cardiomyopathy associated with an apical aneurysm and sustained ventricular tachycardia. She was admitted because of drug refractory ventricular tachycardia. She had been treated with several antiarrhythmic agents, including amiodarone, but symptomatic episodes had continued. Echocardiography, magnetic resonance imaging, and left ventriculography showed mid-ventricular obstructive hypertrophic cardiomyopathy with an apical aneurysm. Electrophysiological study easily reproduced sustained pleomorphic ventricular tachycardia, polymorphic ventricular tachycardia, and ventricular fibrillation. The patient underwent implantation of a cardioverter-defibrillator. The relationship between mid-ventricular hypertrophic cardiomyopathy and apical aneurysm is unknown, but mid-ventricular hypertrophic cardiomyopathy is one of the causes of severe ventricular arrhythmias and sudden death.

Cardiac troponin I level correlates with chronic-phase left ventricular function after successful direct percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: The relationships between cardiac troponin I, various biochemical markers, and chronic-phase left ventricular ejection fraction (LVEF) after successful direct percutaneous transluminal coronary angioplasty (PTCA) were examined in 36 patients with acute myocardial infarction. METHODS: Biochemical markers were measured on admission, immediately after, and from 6 hours to 9 days after PTCA. RESULTS: The time to peak values were: creatine kinase-MB 9.7 hours, cardiac troponin I 9.8 hours, myoglobin 10.7 hours, creatine kinase 10.6 hours, cardiac troponin T 18.6 hours, and myosin light chain 68.9 hours. Cardiac troponin T, cardiac troponin I and myosin light chain levels were elevated over 9 days after successful direct PTCA. Chronic-phase LVEF inversely correlated with peak values of creatine kinase-MB (r = -0.519, p < 0.01), cardiac troponin T (r = -0.500, p < 0.01), cardiac troponin I (r = -0.441, p < 0.05) and creatine kinase (r = -0.411, p < 0.05). The values of cardiac troponin I, cardiac troponin T, creatine kinase and creatine kinase-MB at each sampling point were significantly inversely related to chronic-phase LVEF. The value of cardiac troponin I at each time point for 7 days correlated well with chronic-phase LVEF. CONCLUSIONS: Cardiac troponin I has high specificity for predicting long-term cardiac function after successful direct PTCA when early values are unavailable.

Enhancement of ventricular gradient variability during acute myocardial ischemia.

We evaluated the influence of local myocardial ischemia induced by experimental coronary stenosis on the ventricular gradients (VGs) and determined whether changes of VG were related to the alterations of monophasic action potentials (MAPs). The coronary flow was reduced to 50% in the left anterior descending coronary artery for 30 min in nine dogs. The VG and MAP of consecutive heartbeats over a 20-s interval were obtained from McFee and Parungao body surface leads and a suction electrode on the ischemic and non-ischemic regions. The coefficients of variation of VG and MAP parameters were calculated as indices of variability. The coefficients of variation of the VG magnitude and the MAP area in the ischemic region were greater at 5 min after partial occlusion than in the control period (P < 0.05, P < 0.01, respectively). There was a significant correlation between the coefficient of variation of the VG magnitude and the coefficient of variation of the MAP area in the ischemic region (r = 0.707, P < 0.0001 ) but not in the non-ischemic region. VG variability was enhanced during acute regional ischemia of the ventricular myocardium. VG variability may be caused by enhanced electrical alteration of the MAP in ischemic myocardium.

Callus formation in the humerus compared with the femur and tibia during limb lengthening.

We investigated whether the callus formation in the humerus during the distraction period of limb lengthening proceeds at a higher rate than that in the femur and tibia. Ten achondroplastic patients underwent 3 bilateral humerus, 3 bilateral femur and 4 bilateral tibia lengthenings. To reduce the confounding effect of bone size, we used bone mineral apparent density (BMAD) to compare the three groups; this is a volumetric bone mineral density measurement. BMAD in the distracted callus space was evaluated at 8 weeks after the start of distraction using dual-energy X-ray absorptiometry (mean +/- SD; g/cm3): in the humerus (0.24 +/- 0.08) it was significantly higher than in the tibia (0.10 +/- 0.02), while there was no difference between the humerus and femur (0.35 +/- 0.11). We conclude that the callus formation in the humerus during the distraction period of limb lengthening proceeded at a significantly faster rate than in the tibia, but there was no significant difference between the humerus and femur.

[Long-term beneficial effect of dual chamber pacing in a patient with hypertrophic obstructive cardiomyopathy].

Dual chamber (DDD) pacing therapy was effective to reduce the left ventricular outflow tract pressure gradient for a long time in a patient with pharmacotherapy-resistant hypertrophic obstructive cardiomyopathy. A 52-year-old man with pharmacotherapy-resistant pressure gradient was treated by a DDD pacemaker implantation, because the pressure gradient was proved to be reduced (94-->16 mmHg) by transient DDD pacing with an atrioventricular delay of 50 msec. Hemodynamics and ventricular wall thickness were serially observed after the implantation for 2 years. The pressure gradient progressively decreased during the pacing period, at 4 months and 2 years follow-up, (10-->2 mmHg) and during the sinus rhythm period (60-->25 mmHg), and left ventricular ejection fraction and end-diastolic volume index were increased. Although the ventricular wall thickness remained constant, the systolic anterior motion of the mitral valve and A/E were reduced during the pacing period in the echocardiography. During the acute effect of DDD pacing, the pressure gradient reduction seemed to be related to dilatation of the left ventricular outflow tract induced by a change of contraction modality of the intraventricular septum. Improved left ventricular diastolic function may contribute to the pressure gradient reduction during extended periods of pacing therapy.

Clinical importance of late potential in patients with angina pectoris.

Angina pectoris, especially vasospastic angina, is associated with lethal ventricular tachycardia. The clinical importance of late potential in angina pectoris was assessed in 171 patients with angina-like pain. Patients were categorized into three groups based on coronary angiography. Patients in the exertional angina pectoris (AP) group exhibited at least 75% organic stenosis of a major coronary artery after intracoronary injection of a nitrate drug (82 patients). Patients in the chest pain syndrome (CPS) group had no significant organic stenosis of the coronary artery and the acetylcholine-loading test produced negative results (39 patients). Patients in the vasospastic angina (VSA) group had a positive acetylcholine-loading test (50 patients). When the filtered QRS duration was prolonged to above 130 msec and/or the root-mean-square voltage in the last 40 msec was below 15 microV in VCM-3000, the late potential was judged to be positive. The incidence of late potential was higher in the AP group (23.2%) and the VSA group (38.0%) than in the CPS group (7.7%) (p < 0.05, p < 0.01). Comparison of late potential incidence between patients with coronary vasospasm below 90% (group 1) and patients with above 90% (group 2) induced by the acetyl-choline-loading test in the VSA group showed more late potential in group 2 than in group 1 (84.2% vs 15.8%). Late potential was present in 19 (23.2%) patients in the AP group, but only 2 (10.5%) had under 90% degrees of coronary stenosis and the other 17 (89.5%) had greater than 90% degrees of stenosis. Thus, late potential was mainly observed in patients with severe organic stenosis. These results suggest that the origin of late potential is associated with inhomogeneous electrical excitation induced by frequent angina attack and the duration of total or near total occlusion. Strict clinical management is required for patients with VSA or AP associated with late potential.

Relation between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size in patients with myocardial infarction.

We analyzed signal-averaged electrocardiograms (ECG) obtained in 50 patients with recent myocardial infarction (RMI: 25 anterior and 25 inferior) and 20 normal subjects to determine the relationship between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size. We examined (1) the root mean square voltage (RMS10-40, microV), (2) the integration (A10-40, microV.msec) at 10-msec intervals over the first 40 msec of the signal-averaged QRS complex, and (3) the intervals (T) of the magnitude of the signal-averaged ECG achieved at 10-microV intervals over the first 40 microV (T10-40, msec). The mean RMS10-40 (p < 0.01) and A10-40 (A10, p < 0.05; A20-40, p < 0.01) were significantly lower and the T10-40 (p < 0.01) was significantly longer in RMI patients than in normal subjects. The RMS10-40 (p < 0.01) and A10-40 (p < 0.05) were significantly lower and the T10-40 (T10.20, p < 0.01; T30.40, p < 0.05) was significantly longer in patients with anterior RMI patients than in patients with inferior RMI. The A30 was correlated with the ejection fraction and total creatine kinase (CK) release in all patients (r = 0.73, and -0.78, respectively, p < 0.001). These results suggest that the A30 may be an important predictor of ventricular dysfunction and infarct size in patients with RMI.

Angiotensin-converting enzyme gene polymorphism and cardiovascular endocrine system in coronary angiography patients.

There is continuing interest in the link between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and cardiovascular diseases. Studies on various ethnic populations have shown conflicting evidence as to the association of the DD genotype with an increased risk of myocardial infarction. We examined the relationship between various cardiovascular hormones and ACE gene polymorphism in 149 subjects who underwent cardiac catheterization and had normal cardiac function. The distribution of the II, ID, and DD genotypes was 68, 67, and 14, respectively. Although serum ACE activity was higher in DD and ID than in II (II 9.7+/-0.5 IU/l, ID 12.2+/-0.5, DD 12.8+/-1.2; p < 0.005), other factors of the renin-angiotensin system such as plasma renin activity and plasma concentrations of angiotensin II and aldosterone were not different among the three genotypes. Plasma catecholamines did not differ among the ACE genotypes either, however, plasma atrial natriuretic peptide (ANP) was significantly lower in the subjects carrying the D allele (II 38+/-5 pg/ml, ID 26+/-2, DD 21+/-3; p < 0.05). In particular, the DD genotype showed a low plasma ANP level although the left ventricular mass index was greater than the other genotypes (II 133+/-5 g/m2, ID 137+/-6, DD 165+/-7; p < 0.05). The low plasma ANP in the DD genotype may contribute to the increased risk of cardiovascular diseases.

Callus formation in femur and tibia during leg lengthening: 7 patients examined with DXA.

We examined the callus formation during leg lengthening in 7 achondroplastic patients who underwent 3 bilateral femoral and 4 bilateral tibial lengthenings. Bone mineral content and bone mineral density (BMD) in the lengthened callus space were evaluated every 1 or 2 weeks for 10 weeks after the start of distraction using dual energy X-ray absorptiometry. The mean rate of callus mineralization in femurs (0.64 g/wk) was higher than in tibias (0.22 g/wk). The mean BMD at 10 weeks after the start was 0.35 g/cm2 in the femur and 0.14 g/cm2 in the tibia. Different rates of callus formation in different kinds of long tubular bones have not been reported previously.

Ventricular gradient variability. New ECG method for detection of ischemic heart disease.

The usefulness of ventricular gradient variability for detecting the presence of ischemic heart disease was evaluated in 38 patients with coronary artery disease (group 1), 21 patients with chest pain and no coronary artery disease (group 2), and 33 healthy control subjects. The ventricular gradient of each consecutive heartbeat at rest over a 22-second interval was calculated using a microcomputer. The SD and coefficient of variation for azimuth, elevation, and magnitude were used as indices of ventricular gradient variability. The SD and coefficient of variation of both the magnitude and elevation of ventricular gradient in group 1 were significantly greater than those of the other two groups (P < .01, respectively). When the normal upper limit was defined as 2SD above the mean value in the control group, a comparison between the findings for group 1 and group 2 revealed that the coefficient of variation of magnitude of the ventricular gradient was the most sensitive (82%) and specific (91%) index for coronary artery disease (chi-square test, P < .001). This study suggests that the variability in the magnitude of the ventricular gradient is a reliable index of ischemic heart disease.

[Alteration in ventricular gradient at rest in patients with ischemic heart disease].

The possibility of using alteration in the ventricular gradient (VG) to discern the presence of ischemic heart disease was studied in 30 patients with effort angina pectoris(AP), 21 with vasospastic angina (VSA), 21 with chest pain syndrome (CPS), and 20 healthy volunteers (control). The VG of each consecutive heart beat over a 22-sec interval was calculated by microcomputer from resting Frank-lead X, Y, Z scalar electrocardiograms. The mean values and standard deviations (SD) for the azimuth, elevation, and magnitude of the VG in each group were calculated. The SD and SD/mean ratios for each parameter were used as indices of VG alteration in the groups, and the indices were compared. The SD and SD/mean for the magnitude and elevation of VG were significantly greater in the AP group than in the CPS and control groups. The SD for the azimuth of VG was significantly greater in the AP group than in the CPS and control groups (p < 0.01). The SD and SD/mean for the magnitude of VG were greater in the AP group than in the VSA group (p < 0.01). The SD/mean for the elevation and magnitude of the VG were greater in the VSA group than in the control group (p < 0.01). The SD/mean of the magnitude of the VG was found to be the best index, as it was higher than the upper limit of the control group. The sensitivity and specificity were 80 and 91% (AP vs CPS, p < 0.001), and 43 and 91% (VSA vs CPS, not significant), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intra-atrial injection of colored microspheres on systemic hemodynamics and regional blood flow in rats.

The hemodynamic effects of various numbers of colored nonradioactive microspheres (CMS) and those of accumulation of CMS caused by multiple sequential injection were evaluated in 51 Sprague-Dawley male rats. CMS (15 microns) were injected into the left atrium. Regional blood flow and cardiac output were evaluated using the reference blood sample technique. Ficoll-70 was given after each blood sample withdrawal as a fluid replacement. A bolus injection of < or = 1,000,000 CMS caused no significant hemodynamic disturbances. Amounts of 500,000 CMS can be repeatedly injected up to four times (cumulative dose of 2,000,000 CMS) without producing any adverse hemodynamic effects. The values of cardiac output obtained with the CMS technique were correlated well (r = 0.971, P < 0.0001) with those obtained with electromagnetic flow probes. An excellent reproducibility of organ blood flow was observed after four sequential injections of 500,000 CMS. This study establishes the limits of CMS that can be injected into the rat without inducing hemodynamic changes and also suggests that the CMS technique can be employed to evaluate cardiac output and regional blood flow precisely and repeatedly.

Biochemical components and myocardial performance after reversal of left ventricular hypertrophy in spontaneously hypertensive rats.

OBJECTIVE: This study was undertaken to determine the biochemical and left ventricular functional changes associated with reversal of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). DESIGN: Male SHR and normotensive Wistar-Kyoto (WKY) rats, aged 19 weeks, were treated for 3 weeks with vehicle, amlodipine (10 mg/kg), benazepril (10 mg/kg) or the combination of both agents (4 mg/kg amlodipine and 4 mg/kg benazepril). Left ventricular function was assessed while blood was infused rapidly, at pharmacologically reduced and pretreatment mean arterial pressure (MAP). RESULTS: All treatments reduced MAP and left ventricular mass significantly in SHR. Myocardial protein, RNA and myocardial collagen content were reduced proportionately in all treatment groups in SHR, but not in WKY rats. DNA remained unchanged in all groups. Increased right ventricular mass was produced by amlodipine in both SHR and WKY rats (SHR +11.3%; WKY +9.8%), but this was prevented by cotreatment with benazepril. Right ventricular protein and collagen increased significantly with amlodipine in SHR but not WKY rats, and there were no changes in right ventricular RNA and DNA contents in either strain. Amlodipine improved, benazepril impaired and the combination of both agents maintained left ventricular pumping ability when pressure was increased abruptly to pretreatment levels in WKY rats. In contrast, when afterload was increased abruptly in SHR to pretreatment levels, neither amlodipine nor benazepril affected pumping ability, although it was enhanced by the combination. CONCLUSIONS: These data demonstrate that amlodipine, benazepril and their combination reduced left ventricular mass in SHR. This reversal of LVH was associated with proportional reductions in mycotic protein, RNA and collagen, but not DNA. Therefore, it seems unlikely that LVH reversal with these agents was associated with increased fibrous tissue or impaired left ventricular performance. Finally, addition of the angiotensin converting enzyme inhibitor prevents the increase in right ventricular mass produced by the calcium antagonist.