Compartmentalization of angiotensin II generation in the dog heart. Evidence for independent mechanisms in intravascular and interstitial spaces.

Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 microM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102+/-3 (SEM) to 124+/-3 mmHg (P < 0.01); addition of cap decreased MAP to 95+/-3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101+/-129 to 370+/-158 pg/ml, P < 0.01; and ANG II = 22+/-40 to 466+/-49, P < 0.01); addition of cap further increased ANG I (1,790+/-158, P < 0.01) and decreased ANG II (33+/-49, P < 0.01). ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122+/-528 and 6,333+/-677), during ANG I (8,269+/-502 and 6, 139+/-695) or ANG I + cap (8,753+/-502 and 5,884+/-695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.

Genetic variation in angiotensin-converting enzyme does not prevent development of cardiac hypertrophy or upregulation of angiotensin II in response to aortocaval fistula.

BACKGROUND: Experimental and clinical evidence suggests that angiotensin II may be an important mediator of cardiac hypertrophy in response to hemodynamic stress. We investigated the effect of genetic variation in angiotensin-converting enzyme (ACE) on the development of cardiac hypertrophy and left ventricular (LV) dysfunction in response to volume overload. METHODS AND RESULTS: Male heterozygous ACE knockout (1/0) and wild-type (1/1) mice were studied 4 weeks after the creation of an aortocaval fistula (ACF). The LV weight/body weight ratio increased 74% in ACF versus sham-operated control mice but did not differ between genotypes. Echocardiographic circumferential stress versus rate-corrected velocity of circumferential shortening curves demonstrated depressed LV function in ACF versus sham-operated mice but no difference between genotypes. LV ACE activity was higher in 1/1 versus 1/0 mice and in ACF versus sham-operated mice, and it increased significantly more in the 1/1 versus the 1/0 mice after ACF (P<0.001 for effect of genotype, ACF/sham operation, and interaction term). LV angiotensin II was higher in ACF versus sham-operated mice but did not differ between genotypes, despite 3-fold higher LV ACE activity in ACF 1/1 versus ACF 1/0 mice. CONCLUSIONS: ACE underexpression does not prevent cardiac hypertrophy or LV dysfunction in response to volume overload. LV angiotensin II is unaffected by ACE genotype, both at baseline and after volume overload, indicating that the heart can maintain angiotensin II levels across a broad range of genetic ACE variation under both physiological and pathophysiological conditions.

First transit and equilibrium radionuclide angiography in patients with inferior transmural myocardial infarction: criteria for the diagnosis of associated hemodynamically significant right ventricular infarction.

To define radionuclide criteria for identifying hemodynamically significant right ventricular infarction, 33 consecutive men with inferior transmural infarction were evaluated prospectively by right heart catheterization and first transit and equilibrium radionuclide angiography within 36 hours of the onset of symptoms. Hemodynamically significant right ventricular infarction was present in 6 of the 33 patients (Group I); the remaining 27 patients did not demonstrate the hemodynamics characteristic of right ventricular infarction (Group II). A right ventricular ejection fraction of less than 40% separated Group I and Group II patients by equilibrium (p = 0.003) but not by first transit (p = NS) radionuclide angiography. However, a right ventricular ejection fraction of less than 35% separated Group I and II patients by both techniques (p = 0.02 and p = 0.005, respectively). The presence of a right ventricular regional wall motion abnormality on either first transit or equilibrium radionuclide angiograms separated Group I and II patients (p less than 0.001). The combination of both a right ventricular ejection fraction of less than 40% and a regional wall motion abnormality separated Group I and II patients using either equilibrium (p less than 0.001) or first transit (p = 0.02) radionuclide angiography. It is concluded that in patients with acute inferior transmural myocardial infarction, a right ventricular regional wall motion abnormality alone or in combination with a right ventricular ejection fraction of less than 40% by either first transit or equilibrium radionuclide angiography is a useful criterion for establishing the presence of hemodynamically significant right ventricular infarction, while its absence argues against the diagnosis of right ventricular infarction.

Right ventricular infarction: identification by hemodynamic measurements before and after volume loading and correlation with noninvasive techniques.

To evaluate the potential occurrence of right ventricular infarction, 53 patients with acute inferior transmural myocardial infarction were studied within 36 hours of symptoms by right heart catheterization, equilibrium radionuclide angiography and two-dimensional echocardiography. Technetium-99m pyrophosphate myocardial scintigraphy was performed 3 days after the onset of symptoms. The hemodynamic standard for right ventricular infarction was defined as both a right atrial pressure of 10 mm Hg or more and a right atrial/pulmonary artery wedge pressure ratio of 0.8 or more. Eight (15%) of the 53 patients had hemodynamic measurements at rest characteristic of right ventricular infarction, and 6 (11%) additional patients met these criteria after volume loading (p less than 0.05). Nineteen (37%) of the 51 patients who had radionuclide angiography had right ventricular dysfunction manifested by both a reduced right ventricular ejection fraction (less than 40%) and right ventricular regional wall motion abnormalities (akinesia or dyskinesia). An abnormal radionuclide angiogram was observed in 12 of 13 patients with hemodynamic measurements indicating right ventricular infarction. In 12 patients with an abnormal radionuclide angiographic study, right ventricular ejection fraction improved 6 to 12 weeks after infarction (27 +/- 7 to 36 +/- 9%, p less than 0.01). Twenty-two (49%) of the 45 patients with adequate two-dimensional echocardiograms had a right ventricular regional wall motion abnormality. An abnormal two-dimensional echocardiogram was seen in 9 of 11 patients with hemodynamic measurements characteristic of right ventricular infarction. Technetium-99m pyrophosphate scintigraphy was positive for right ventricular infarction in 3 of 12 patients who had hemodynamic measurements indicating right ventricular infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Accurate estimates of absolute left ventricular volumes from equilibrium radionuclide angiographic count data using a simple geometric attenuation correction.

To simplify and clarify the methods of obtaining attenuation-corrected equilibrium radionuclide angiographic estimates of absolute left ventricular volumes, 27 patients who also had biplane contrast cineangiography were evaluated. Background-corrected left ventricular end-diastolic and end-systolic counts were obtained by semiautomated variable and hand-drawn regions of interest and were normalized to cardiac cycles processed, frame rate and blood sample counts. Blood sample counts were acquired on (d degree) and at a distance (d') from the collimator. A simple geometric attenuation correction was performed to obtain absolute left ventricular volume estimates. Using blood sample counts obtained at d degree or d', the attentuation-corrected radionuclide left ventricular end-diastolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-diastolic volumes (r = 0.95 to 0.96). However, both mean radionuclide semiautomated variable left ventricular end-diastolic volumes (179 +/- 100 [+/- 1 standard deviation] and 185 +/- 102 ml, p less than 0.001) were smaller than the average cineangiographic end-diastolic volume (217 +/- 102 ml), and both mean hand-drawn left ventricular end-diastolic volumes (212 +/- 104 and 220 +/- 106 ml) did not differ from the average cineangiographic end-diastolic volume. Using the blood sample counts obtained at d degree or d', the attenuation-corrected radionuclide left ventricular end-systolic volume estimates using both region of interest selection methods correlated with the cineangiographic end-systolic volumes (r = 0.96 to 0.98). Also, using blood sample counts at d degree, the mean radionuclide semiautomated variable left ventricular end-systolic volume (116 +/- 98 ml, p less than 0.05) was less than the average cineangiographic end-systolic volume (128 +/- 98 ml), and the other radionuclide end-systolic volumes did not differ from the average cineangiographic end-systolic volume. Therefore, it is concluded that: 1) a simple geometric attenuation-correction of radionuclide left ventricular end-diastolic and end-systolic count data provides accurate estimates of biplane cineangiographic end-diastolic and end-systolic volumes; and 2) the hand-drawn region of interest selection method, unlike the semiautomated variable method that underestimates end-diastolic and end-systolic volumes, provides more accurate estimates of biplane cineangiographic left ventricular volumes irrespective of the distance blood sample counts are acquired from the collimator.

Handgrip increases endothelin-1 secretion in normotensive young male offspring of hypertensive parents.

OBJECTIVES: We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents. BACKGROUND: It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension. METHODS: Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery. RESULTS: Group A had higher norepinephrine levels than group B throughout the test (baseline 181+/-32 [SEM] vs. 96+/-12 pg/ml, p < 0.05; peak HG 467+/-45 vs. 158+/-12 pg/ml, p < 0.000001; R2 293+/-46 vs. 134+/-8 pg/ml, p < 0.01; RO1 214+/-27 vs. 129+/-10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07+/-0.14 vs. 0.59+/-0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88+/-0.31 vs. 0.76+/-0.09 pg/ml, p < 0.005) and R2 (2.46+/-0.57 vs. 1.31+/-0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16+/-0.78 vs. 0.52+/-0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square=7.59, p=0.0059) and ET-1 changes during HG (chi-square=4.23, p=0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not. CONCLUSIONS: The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.

Angiotensin-converting enzyme inhibitor therapy affects left ventricular mass in patients with ejection fraction > 40% after acute myocardial infarction.

OBJECTIVES: We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy decreases left ventricular (LV) mass in patients with a left ventricular ejection fraction (LVEF) > 40% and no evidence of heart failure after their first acute Q wave myocardial infarction (MI). BACKGROUND: Recently, ACE inhibitor therapy has been shown to have an early mortality benefit in unselected patients with acute MI, including patients without heart failure and a LVEF > 35%. However, the effects on LV mass and volume in this patient population have not been studied. METHODS: Thirty-five patients with a LVEF > 40% after their first acute Q wave MI were randomized to titrated oral ramipril (n = 20) or conventional therapy (control, n = 15). Magnetic resonance imaging (MRI) performed an average of 7 days and 3 months after MI provided LV volumes and mass from summated serial short-axis slices. RESULTS: Left ventricular end-diastolic volume index did not change in ramipril-treated patients (62 +/- 16 [SD] to 66 +/- 17 ml/m2) or in control patients (62 +/- 16 to 68 +/- 17 ml/m2), and stroke volume index increased significantly in both groups. However, LV mass index decreased in ramipril-treated patients (82 +/- 18 to 73 +/- 19 g/m2, p = 0.0002) but not in the control patients (77 +/- 15 to 79 +/- 23 g/m2). Systolic arterial pressure did not change in either group at 3-month follow-up. CONCLUSIONS: In patients with a LVEF > 40% after acute MI, ramipril decreased LV mass, and blood pressure and LV function were unchanged after 3 months of therapy. Whether the decrease in mass represents a sustained effect that is associated with a decrease in morbid events requires further investigation.

Application of a time varying elastance model to right ventricular performance in man.

To evaluate instantaneous right ventricular pressure-volume relations we studied nine patients with normal coronary anatomy and ventricular function with simultaneous high fidelity pressure, flow-velocity, and biplane cineventriculographic volumes (60 frames.s-1) during atrial pacing at 93(SD5) beats-min-1, partial autonomic blockade, and pharmacologically altered ventricular loading. The maximum time varying elastance, Emax, was defined as the maximum slope of isochronal, simultaneous pressure-volume data points derived by linear regression analysis from three loading conditions. The slope of the non-isochronal maximum pressure/volume ratio, pressure at minimum volume, end ejection pressure/volume, and peak right ventricular pressure/minimum volume were also derived from the three loading conditions. The mean slope for Emax was 1.30(0.84) mm Hg.ml-1 (range 0.62-2.87) and the volume axis intercept at zero pressure (Vo) was 46(21) ml (range 24-89 ml). Time dependent Emax was characterised by a series of parallel shifting lines of best fit with large changes in Vo in addition to changes in the slope of the pressure volume relations. Only maximum pressure/volume ratio and peak pressure/minimum volume were linearly related to Emax (r = 0.82 and 0.84 respectively, p = 0.05) while pressure at minimum volume and end ejection pressure/volume did not correlate with Emax. We conclude that in normal human subjects (1) right ventricular systolic function may be approximated using a time varying elastance model characterised by a time dependent Vo; (2) end systolic pressure-volume relations using maximum pressure/volume ratio and peak pressure/minimum volume systematically estimate Emax; and (3) other right ventricular end systolic pressure-volume relations near end ejection bear no obvious relation to Emax because of the wide temporal separation between peak systolic elastance and end ejection in this chamber.

A stable model of left ventricular dysfunction in an intact animal assessed with high fidelity pressure and cinemagnetic resonance imaging.

OBJECTIVE: Numerous models of acute and chronic left ventricular dysfunction have been used over the years. However, few can produce a rapid onset of global systolic and diastolic dysfunction that is stable and potentially reversible. The aim of this study was to develop such a model. METHODS: A model of left ventricular dysfunction was produced in six intact dogs using 1% halothane anaesthesia and pharmacological autonomic blockade with atropine (0.1 mg.kg-1) and propranolol (2 mg.kg-1). Left ventricular function was assessed by combined high fidelity pressure and cinemagnetic resonance imaging (cine-MR) during increases in afterload using infusions of angiotensin. RESULTS: Left ventricular systolic dysfunction was characterised by a diminished resting ejection fraction of 45(SD 4)% and a depressed +dP/dtmax of 1537(100) mm Hg.s-1. Diastolic dysfunction was manifested by an increased left ventricular end diastolic pressure of 16(2) mm Hg, a decreased -dP/dtmax of -1705(369) mm Hg.s-1, and a prolonged time constant of left ventricular relaxation of 42(9) ms. As left ventricular systolic pressure steadily rose with angiotensin infusion from 87(7) to 124(13) to 152(10) mm Hg (p < 0.001), left ventricular ejection fraction decreased markedly from 45(4) to 35(4) to 27(4)% (p < 0.001). Left ventricular +dP/dtmax did not change [1537(100) to 1500(110) to 1498(84) mm Hg.s-1] in spite of a significant increase in left ventricular end diastolic pressure from 16(2) to 21(5) to 29(7) mm Hg (p < 0.001) and left ventricular end diastolic volume from 59(12) to 71(14) to 78(17) ml (p < 0.001). Individual slopes of the end systolic pressure-volume relationship were also low, ranging between 2.1 and 4.4 mm Hg.s-1 (r = 0.99 to 1.00), typical of impaired contractility. CONCLUSIONS: Halothane anaesthesia in dogs pretreated with large amounts of propranolol and appropriate muscarinic cholinergic blockade produces a moderate decrease in baseline systolic and diastolic function in our intact dog model. However, left ventricular systolic function showed limited contractile reserve when challenged by physiological increases in systemic arterial pressure. Impaired systolic and diastolic function may, at least in part, be related to diminished activator calcium produced by halothane in addition to the well known negative inotropic action of beta adrenergic blockade.

Ventricular coupling via the pericardium: normal versus tamponade.

OBJECTIVE: The aim was to examine how regional variations in pericardial pressure affect the mechanical coupling between the ventricles. METHODS: Canine hearts from 14 dogs (14.5-18 kg) were removed and placed in cold cardioplegia solution. Balloons were inserted into the left and right ventricles and the atria. Pericardial pressure over the left ventricle (Pclv) and the right ventricle (Pcrv) was measured with thin balloon catheters. Ventricular and pericardial pressures were measured, and ventricular and pericardial coupling was calculated, under control conditions and with increases in pericardial tension and fluid. RESULTS: At baseline, regional differences in pericardial pressure occurred [Pclv > Pcrv, 4.0(SD 0.9) v 2.9(0.6) mm Hg, p < 0.05]. Ventricular coupling via the pericardium was defined as delta Pclv/delta Pcrv for right ventricular volume increases and delta Pcrv/delta Pclv for left ventricular volume increases. This ratio increased more after increasing right ventricular volume than after increasing left ventricular volume [delta Pclv/delta Pcrv > delta Pcrv/delta Pclv, 1.14(0.33) v 0.51(0.15), p < 0.05]. Increasing the pericardial tension by clamping the pericardium increased pericardial pressures, yet did not alter the regional variations in pressure [Pclv > Pcrv, 8.4(2.2) v 6.4(2.5) mm Hg, p < 0.05] or pericardial coupling [delta Pclv/delta Pcrv > delta Pclv/delta Pcrv, 1.18(0.46) v 0.54(0.16), p < 0.05]. In contrast, creating a mild tamponade increased pericardial pressures, eliminated regional differences in pressure, and altered the coupling between ventricles [delta Pclv/delta Pcrv approximately delta Pclv/delta Pcrv, 0.95(0.11) v 1.05(0.08), p = NS]. These regional differences in pericardial pressure might have a geometrical basis. In four in vivo canine experiments using cine magnetic resonance, the short axis radius of curvature for the right ventricle was greater than for the left ventricle [38.3(4.4) mm v 29.2(3.8) mm, p < 0.05]. CONCLUSIONS: The pericardium partially protects right ventricular filling: regional differences in pericardial pressure normally occurred with lower pericardial pressure over the right ventricle, and left to right ventricular coupling was less. This protection of right ventricular filling was lost with even a small pericardial effusion.

Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy.

We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure. In this substudy, we investigated the effect of mineralocorticoid receptor blockade with spironolactone on pre-clinical diastolic dysfunction. Thirty-four patients (19 with high and 15 with normal aldosterone levels) were treated with spironolactone and followed with cardiac magnetic resonance with tissue tagging at baseline, 3 and 6 months of treatment. Serum markers of collagen turnover (C-propeptide of type-I procollagen and carboxy-terminal telopeptide of type-I collagen) were measured at baseline and at 6 months. At baseline, patients demonstrated reduced E/A ratio (volumetric normalized peak early filling rate/late filling rate, normalized to left ventricular end-diastolic volume), lower peak early-diastolic mitral annular velocity and lower peak early-diastolic circumferential strain rates compared to the reference values obtained from 45 normal controls without HTN or cardiac disease (all comparisons, P<0.01). No significant change occurred in diastolic filling, relaxation parameters or collagen markers with spironolactone therapy at 6 months irrespective of aldosterone status despite significant reduction in left ventricular mass index in both high- and normal-aldosterone groups. In conclusion, resistant HTN patients with LVH demonstrate significant pre-clinical diastolic dysfunction. Short-term spironolactone therapy may not lead to improvement in diastolic function despite rapid reversal of LVH.

Enalaprilat blunts reflexive increases in cardiac interstitial norepinephrine in conscious rats.

OBJECTIVE: We have reported that acute administration of enalaprilat, an angiotensin converting enzyme inhibitor, induces less reflexive increase in lumbar sympathetic nerve activity in spontaneously hypertensive rats (SHRs) than nicardipine, a dihydropyridine calcium-channel blocker. The current study was conducted to determine if angiotensin converting enzyme inhibitors likewise suppress cardiac sympathetic activation. DESIGN: Cardiac interstitial levels of norepinephrine were measured in fully conscious SHRs before and after acute blood pressure lowering with enalaprilat or nicardipine. METHODS: Microdialysis probes were inserted into the left ventricular wall of SHRs. Twenty-four to 48 hours post-implantation, myocardial interstitial fluid was collected in fully conscious rats during a 60-min baseline period. Mean arterial pressure was lowered 20 mmHg with intravenous infusion of enalaprilat or nicardipine. During continuous enalaprilat or nicardipine infusion, myocardial interstitial fluid was again collected. Norepinephrine levels were assayed in the perfusate. CONCLUSIONS: Enalaprilat-induced reduction in mean arterial pressure did not significantly increase cardiac interstitial norepinephrine levels. In contrast, nicardipine-induced reduction in blood pressure was associated with a significant increase in interstitial norepinephrine levels. These results indicate that enalaprilat suppresses reflexive sympathetic activation of the heart during acute blood pressure lowering. These results may be clinically relevant in that reductions in end-organ sympathetic stimulation may enhance the long-term cardiovascular benefit of angiotensin converting enzyme inhibitors.

Assessment of the radionuclide angiographic left ventricular maximum time-varying elastance calculation in man.

This investigation was designed to determine whether left ventricular (LV) maximum time-varying elastance (Emax) calculations obtained using equilibrium radionuclide angiography (RNA) were comparable to those obtained using biplane contrast cineangiography (CINE), and whether simple, indirect P-V relations might provide reasonable, alternative estimates of Emax. Accordingly, we studied 19 patients with simultaneous high-fidelity micromanometer LV and fluid brachial artery (Ba) pressure recordings, CINE, and RNA under control conditions and during methoxamine and nitroprusside infusions. Emax was defined for CINE and RNA as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. The indirect P-V relations were similarly obtained from Ba peak (P) pressure versus minimum RNA LV volume (BaP/minV) and Ba dicrotic notch (di) pressure versus minimum RNA LV volume (Badi/minV) data points. The mean heart rates and LV (+)dP/dtmax values were minimally altered during the three loading conditions. The isochronal Emax values ranged from 1.40 to 6.73 mmHg/ml (mean 4.13 +/- 1.99 s.d. mmHg/ml) for CINE and from 1.48 to 7.25 (mean 4.35 +/- 1.81 mmHg/ml) for RNA (p = N.S.). Similarly, the unstressed volumes ranged from -10 to 80 ml (mean 30 +/- 23 ml) for CINE and from -8 to 77 ml (29 +/- 21 ml) for RNA (p = N.S.). The individual, isochronal Emax values by RNA correlated with those by CINE (r = 0.86). In 14 of the 19 patients, the BaP/minV and Badi/minV relations correlated with the isochronal Emax values calculated by RNA (r = 0.83 and 0.82, respectively), and these relations also correlated with the Emax values calculated by CINE (r = 0.82 and 0.78, respectively). The slope and V0 values for the BaP/minV and Badi/minV relations underestimated those for Emax by RNA and CINE (p less than 0.01 and p less than 0.05, respectively, for both). Thus, the isochronal Emax values calculated using RNA are comparable to those obtained using CINE in man. Moreover, indirect P-V relations underestimate these Emax values, but they are linearly related with the isochronal Emax values calculated by RNA and CINE. Consequently, these indirect P-V relations may provide a more simple, alternative estimate of LV contractile function in man.

Estimates of left-ventricular volumes by equilibrium radionuclide angiography: importance of attenuation correction.

To compare the accuracy of attenuated and attenuation-corrected equilibrium radionuclide angiographic (RNA) left ventricular (LV) volume estimates, we studied 23 consecutive patients with biplane contrast cineangiography (CINE). Attenuated RNA end-diastolic (ED) and end-systolic (ES) volumes were calculated from background-corrected ED and ES counts obtained from hand-drawn regions of interest that were normalized to cardiac cycles processed, frame rate, and blood activity. A simple, geometric attenuation correction was performed to obtain attenuation-corrected RNA LV volumes. The attenuated and attenuation-corrected RNA LV EDV estimates correlated with the CINE LV EDVs ; however, the attenuation-corrected RNA LV EDV estimates correlated more closely. Also, the average attenuation-corrected RNA LV EDV did not differ significantly from the mean CINE LV EDV. Attenuated and attenuation-corrected RNA LV ESV estimates also correlated with the CINE LV ESVs , but the attenuation-corrected RNA LV ESV estimates correlated more closely. Also, the average attenuation-corrected RNA LV ESV did not differ significantly from the mean biplane CINE LV ESV.

Mechanism of postextrasystolic potentiation in the right ventricle.

The mechanism of postextrasystolic potentiation (PESP) has been studied in the left ventricle in humans; however, this phenomenon has not been evaluated in the right ventricle. Accordingly, 18 sinus beats were compared to postextrasystolic beats during the same cineventriculogram using simultaneous high-fidelity right ventricular (RV) and pulmonary artery pressures and cast-validated biplane cineventriculographic volumes in normal patients. The increase in cycle length was 22 +/- 12% (standard deviation) in the postextrasystolic beats. Right ventricular ejection fraction increased from 61 +/- 10 to 68 +/- 4% (p less than 0.001) and RV stroke volume increased from 99 +/- 18 to 128 +/- 20 ml (p less than 0.001) due to an increase in RV end-diastolic volume (165 +/- 34 to 189 +/- 30 ml, p less than 0.001) as RV end-systolic volume (65 +/- 24 to 61 +/- 17 ml, difference not significant) and RV end-systolic pressure (16 +/- 7 to 17 +/- 6 mm Hg, difference not significant) remained unchanged. Despite an increase in RV systolic pressure from 29 +/- 7 to 31 +/- 7 mm Hg (p less than 0.01) and an increase in RV end-diastolic pressure from 8 +/- 4 to 10 +/- 5 mm Hg (p less than 0.001), RV +dP/dtmax did not change (318 +/- 102 to 294 +/- 82 mm Hg/s, difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous metoprolol on left ventricular performance in Q-wave acute myocardial infarction.

To determine the effects of intravenous metoprolol on left ventricular (LV) function in acute myocardial infarction (AMI), 16 patients were studied within 48 hours of Q-wave AMI (mean ejection fraction 47 +/- 6%, mean pulmonary artery wedge pressure 22 +/- 6 mm Hg) with high fidelity pressure and biplane cineventriculography before and after intravenous metoprolol (dose 12 +/- 4 mg). Heart rate decreased from 90 +/- 13 to 74 +/- 11 beats/min (p less than 0.001), pulmonary arterial wedge pressure and LV end-diastolic pressure were unchanged (22 +/- 6 to 21 +/- 6 and 27 +/- 8 to 26 +/- 8 mm Hg, respectively), despite impaired LV relaxation (P = Poe-t/T) after intravenous metoprolol (T from 59 +/- 13 to 72 +/- 12 ms, p less than 0.001). Peak systolic circumferential LV wall stress decreased after beta-adrenergic blockade (330 +/- 93 to 268 +/- 89 g/cm2, p less than 0.05) and LV contractility decreased (dP/dtmax from 1,480 +/- 450 to 1,061 +/- 340 mm Hg/s, p less than 0.001). The ejection fraction decreased (48 +/- 7 to 43 +/- 7%, p less than 0.05) due to an increase in LV end-systolic volume (85 +/- 19 to 93 +/- 19 ml, p less than 0.05) since LV end-diastolic volume was unchanged (161 +/- 30 to 163 +/- 30 ml, difference not significant). In patients with Q-wave AMI, intravenous metoprolol reduces the major determinants of myocardial oxygen demand including heart rate, contractility and peak systolic wall stress. Further, despite decreased heart rate, (+)dP/dtmax, ejection fraction, isovolumic relaxation, LV end-diastolic pressure and end-diastolic volume remain unchanged.

Usefulness of two-dimensional echocardiography during low-level exercise testing early after uncomplicated acute myocardial infarction.

To determine whether 2-dimensional (2-D) echocardiographic measures of segmental and global left ventricular (LV) function immediately on recovery of low-level, symptom-limited treadmill exercise are as sensitive as the same variables measured at peak bicycle exercise, 21 patients were studied after acute myocardial infarction (AMI). The recovery treadmill ejection fraction analysis was predictive of the peak bicycle results in 18 of the 21 patients (86%) and recovery treadmill wall motion abnormalities were predictive of the peak bicycle analysis in 17 (81%) (p less than 0.01). These data indicate that 2-D echocardiography during the immediate recovery phase of low-level postinfarction treadmill testing was as sensitive as the peak exercise assessment of segmental and global LV function. Accordingly, the predictive value of rest and recovery exercise measures were prospectively assessed in 67 patients during a mean follow-up interval of 11 months (range 3 to 24). Clinical characteristics and treadmill electrocardiographic findings did not identify the 16 of 67 patients (24%) who had new cardiac events (3 cardiac deaths, 8 recurrent AMIs and 6 coronary artery bypass graft operations). However, a decrease in recovery ejection fraction units of more than 10% was seen in 7 of these 16 patients (44%) with events, compared with only 4 of the 51 (13%) without events (p less than 0.002), and new or worsening wall motion abnormalities on exercise recovery were seen in 10 of the 16 patients (63%) with events, but in only 10 of the 51 (20%) without (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Isometric handgrip exercise increases endothelin-1 plasma levels in patients with chronic congestive heart failure.

This study demonstrated an immediate and short-lasting endothelin-1 release in the circulation of patients with severe chronic congestive heart failure during isometric handgrip exercise, but not in normal subjects. Our data suggest that endothelin-1 levels may increase transiently during daily physical activity, thus contributing to progressive deterioration of left ventricular function.

Accuracy of biplane long-axis left ventricular volume determined by cine magnetic resonance imaging in patients with regional and global dysfunction.

Left ventricular (LV) volumes and ejection fraction can be obtained by applying Simpson's rule to multiple short-axis tomographic planes. A simpler method for determining LV volumes using the area-length equation is widely accepted and requires less time to acquire and analyze. Its accuracy, however, is questionable in deformed or asymmetrically contracting ventricles. This study compares biplane long-axis to serial short-axis computed LV volumes obtained by cine gradient-echo magnetic resonance imaging (MRI) in 2 distinct patient populations: (1) patients with global LV dysfunction, and (2) patients with regional LV dysfunction. A total of 114 patients were studied using both methods. Among 37 patients with global LV dysfunction, there was no statistically significant difference between methods (long axis vs short axis) for determining LV end-diastolic volume (203 +/- 91 vs 201 +/- 90 ml), end-systolic volume (142 +/- 81 vs 141 +/- 82 ml), and ejection fraction (33 +/- 12 vs 33 +/- 13%). However, in the 77 patients with regional dysfunction, LV end-diastolic volume was statistically slightly higher when obtained using the long-axis approach (157 +/- 53 vs 152 +/- 51 ml; p=0.004). Otherwise, end-systolic volume (97 +/- 49 vs 95 +/- 49 ml) and ejection fraction (40 +/- 13 vs 40 +/- 13%) were similar (p=NS). The correlation between LV volumes and ejection fractions for both groups was excellent (r >0.91). Thus, in this study group, biplane long-axis and serial short-axis computed LV volumes and ejection fractions were similar in patients with global or regional LV dysfunction. In critically ill patients unable to complete a comprehensive MRI examination, the biplane long-axis-derived volumes provide adequate data.

Cardiac function and functional capacity: implications for the failing heart.

The exercise capacity of patients with congestive heart failure is determined by factors including the interaction of the right and left ventricles and their respective circulations, lung mechanics, skeletal muscle metabolism, and blood flow. Therapeutic efforts should be directed at all of the units in this complex process rather than the response of an individual system. Multiple therapeutic regimens such as nitrates and angiotensin converting enzyme inhibitors in combination with physical training and other therapies that improve pulmonary function produce optimal results. Using this holistic approach to therapy, the physician may have a beneficial impact on the exercise capacity of patients with congestive heart failure.