Sardinian alcohol-preferring rats prefer chocolate and sucrose over ethanol

The purpose of this study was to evaluate the effect of sequential external counterpulsation (SECP) on cerebral and renal blood flow. The effect of SECP on carotid and renal artery blood flow was studied in 35 and 18 patients, respectively. With a portable unit, cuffs were applied to the calves and thighs, sequentially inflated with air at the onset of diastole, and deflated at the onset of systole. Carotid and renal artery Duplex studies were performed during intermittent SECP. Flow velocity and flow velocity integral were measured at baseline and during SECP. Diastolic augmentation of carotid and renal artery flow velocity was observed in all patients. The mean carotid flow velocity integral increased by 22% from 27.7 +/- 1.8 cm to 33.1 +/- 2.3 cm (P = 0.001). The mean renal artery flow velocity integral increased by 19% from 21 +/- 1 cm to 25 +/- 1 cm (P = 0.0001). With SECP, a new diastolic Doppler flow velocity wave was observed, with an average peak carotid diastolic flow velocity of 56 +/- 4 cm/sec and an average peak renal artery diastolic flow velocity of 40 +/- 2.5 cm/sec. This diastolic wave was 75% (carotid) and 68% (renal) as high as the systolic wave during SECP. In addition, with SECP the systolic wave increased by 6% and 8% in the carotid and renal artery, respectively (P = 0.02 and 0.006, respectively). In conclusion, SECP significantly increases carotid and renal blood flow. This noninvasive, harmless treatment may be useful to support patients with decreased cerebral and renal perfusion.     

Effects of partial left ventriculectomy on left ventricular performance in patients with nonischemic dilated cardiomyopathy

OBJECTIVES: This study sought to assess the effects of partial left ventriculectomy (PLV) on left ventricular (LV) performance in a series of consecutive patients with nonischemic dilated cardiomyopathy. BACKGROUND: Reduction of LV systolic function in patients with heart failure is associated with an increase of LV volume and alteration of its shape. Recently, PLV, a novel surgical procedure, was proposed as a treatment option to alter this process in patients with dilated cardiomyopathy. METHODS: We studied 19 patients with severely symptomatic nonischemic dilated cardiomyopathy, before and 13+/-3 days after surgery, and 12 controls. Single-plane left ventriculography with simultaneous measurements of femoral artery pressure was performed during right heart pacing. RESULTS: The LV end-diastolic and end-systolic volume indexes decreased after PLV (from 169 to 102 ml/m2, and from 127 to 60 ml/m2, respectively, p < 0.0001 for both). Despite a decrease in LV mass index (from 162 to 137 g/m2, p < 0.0001), there was a significant decrease in LV circumferential end-systolic and end-diastolic stresses (from 277 to 159 g/cm2, p < 0.0001 and from 79 to 39 g/cm2, p = 0.0014, respectively). Ejection fraction improved (from 24% to 41%, p < 0.0001); the stroke work index remained unchanged. CONCLUSIONS: The PLV improves LV performance by a dramatic reduction of ventricular end-systolic and end-diastolic stresses. Further studies are needed to assess whether this effect is sustained during long-term follow-up and to define the role of PLV in the treatment of patients with dilated cardiomyopathy.     

Doppler analysis of pulmonary venous flow profiles in orthotopic heart transplant recipients: a comparison with mitral flow profiles and atrial function

Previous Doppler studies of transmitral flow profiles in heart transplant recipients suggested left ventricular (LV) diastolic dysfunction. The influence of left atrial filling and emptying on mitral Doppler profiles in heart transplant recipients has not been studied systematically. In the present study, pulmonary venous flow profiles, mitral flow profiles, left atrial area change and mitral annulus motion were analyzed in 20 orthotopic heart transplant recipient and 20 control subjects by transthoracic and transesophageal echocardiography and Doppler. Mitral flow profiles revealed a "restrictive" pattern with a high early-to-late diastolic flow velocity ratio in transplant patients (2.16 +/- 0.52 vs. 1.30 +/- 0.25, p < 0.0001), which was mainly due to a reduced late diastolic maximum mitral flow velocity (32.6 +/- 8.3 vs. 51.6 +/- 12.4 cm/s, p < 0.0001). Left atrial area change (35.9 +/- 13.9 vs. 58.1 +/- 17.0%, p < 0.0006) and mitral annulus motion (9.2 +/- 3.3 vs. 12.2 +/- 2.0%, p < 0.05) were reduced in transplant recipients, compared to controls. Pulmonary venous flow parameters in transplant recipients were markedly altered during systole, when pulmonary venous flow parameters are influenced primarily by atrial function rather than by diastolic LV properties: peak systolic flow velocity (45.5 +/- 8.2 vs. 62.3 +/- 14.0 cm/s, p < 0.001), maximum flow velocity ratio (0.87 +/- 0.19 vs. 1.45 +/- 0.33), time velocity integral of pulmonary venous flow during systole (9.3 +/- 2.3 vs. 17.1 +/- 4.0 cm, p < 0.001) and the systolic fraction of the time velocity integral (52.6 +/- 10.8 vs. 68.5 +/- 6.8%, p < 0.001) were lower in heart transplant recipients than in controls. These findings are compatible with atrial dysfunction and reduced mitral annulus motion. The results of this study indicate that LV diastolic dysfunction is not the only possible cause of altered transmitral Doppler profiles in heart transplant recipients. Atrial abnormalities represent a major contributing factor to altered mitral and pulmonary venous flow patterns. Analysis of transmitral Doppler profiles alone are therefore not adequate for analysis of diastolic LV function in heart transplant recipients.     

Left ventricular diastolic properties of hypertensive patients measured by pulsed tissue Doppler imaging

Examination of left ventricular (LV) diastolic dysfunction in hypertensive patients has been based on parameters obtained from the transmitral flow velocity during pulsed Doppler echocardiography. However, these parameters are affected by loading conditions. We evaluated LV diastolic function along the longitudinal and transverse axes by pulsed tissue Doppler imaging (TDI) in 50 hypertensive (HT) patients and 36 age-matched healthy volunteers (N). Transmitral flow velocity was recorded by pulsed Doppler echocardiography. LV posterior wall motion velocity along the longitudinal and transverse axes also was recorded by pulsed TDI. In both groups, peak early diastolic velocity of the LV posterior wall (Ew) along the transverse axis (N: 15.8+/-5.2 cm/s, HT: 12.2+/-4.4 cm/s) was higher than that along the longitudinal axis (N: 12.7+/-3.1 cm/s, HT: 9.5+/-3.3 cm/s). Peak atrial systolic velocity of the LV posterior wall (Aw) along the longitudinal axis (N: 9.1+/-1.8 cm/s, HT: 9.7 +/-2.6 cm/s) significantly exceeded that along the transverse axis (N: 8.0+/-2.2 cm/s, HT: 8.4+/-2.4 cm/s) in both groups. The Ews were lower and the Aws were higher along both axes in the patient group than in the control group. The time intervals from the aortic component of the second heart sound to the peak of the early diastolic wave (IIA-Ews) along both the transverse (N: 142+/-18 ms, HT: 154+/-19 ms) and longitudinal (N: 151 16 ms, HT: 162+/-20 ms) axes were longer in the patient group. In 29 patients, Ews along both axes correlated negatively (transverse: r = -0.80, P < .0001; longitudinal: r = -0.71, P < .0001) and IIA-Ews correlated positively (transverse: r = 0.81, P < .0001; longitudinal: r = 0.74, P < .001) with the time constant of the LV pressure decay during isovolumic diastole. The Aws along both axes in the 24 patients without pseudonormalization in transmitral flow velocity correlated positively (transverse: r = 0.60, P < .001; longitudinal: r = 0.74, P < .0001) with the LV end-diastolic pressure. In conclusion, LV relaxation and filling along the longitudinal and transverse axes were impaired in many patients with hypertension. Pulsed TDI was useful for evaluating LV diastolic dynamics in this disease.     

Mechanisms of nitrate accumulation in plasma during pacing-induced heart failure in conscious dogs

The goal of this study was to understand the mechanisms behind the changes in plasma NOx during heart failure. Heart failure is associated with an increase in plasma nitrate levels, and yet most experimental evidence demonstrates a reduction in endothelial nitric oxide production during heart failure. Dogs were chronically instrumented for measurement of systemic hemodynamics and left ventricular (LV) dimensions. Hearts were paced at 210 bpm for 3 weeks (n = 14) and then 240 bpm for 1 week (n = 7). Hemodynamics, arterial blood gases, plasma NOx, and creatinine levels were monitored weekly. Heart failure was evidenced by cachexia, ascites, and hemodynamic alterations. Resting heart rate rose (94 +/- 6 to 135 +/- 9 bpm), and LV dP/dt fell (2810 +/- 82 to 1471 +/- 99 mm Hg/s), while LV end diastolic pressure quadrupled (5.8 +/- 0.7 to 25 +/- 0.8 mm Hg), and diastolic wall stress quadrupled (11 +/- 1.3 to 43 +/- 6.0 g/cm2, all P < 0.05). These changes occurred during a doubling in plasma NOx (5.5 +/- 1.5 to 10 +/- 1.6 microM, P < 0.05). There were no changes in plasma NOx through 3 weeks of pacing. Plasma creatinine levels increased 450% (from 0.27 +/- 0.32 to 1.21 +/- 0.63 mg%). Stimulated nitrite production by agonists in sieved coronary microvessels was unchanged after 3 weeks of pacing but was reduced after heart failure. Plasma NOx did not correlate with LV dP/dt or systolic wall stress but correlated directly with LV EDP or diastolic wall stress and inversely with cardiac work. Plasma NOx rose in direct relation to plasma creatinine levels (Y = 4.8X + 2.8, r2 = 0.84), suggesting that the rise in plasma NOx during heart failure is due to decreased renal function not increased NO production.     

Genetics of kidney tumours

BACKGROUND: Allograft rejection in heart transplant recipients is associated with lymphocytic extracellular infiltration and edema resulting in increased myocardial stiffness and abnormal relaxation. We hypothesize that these abnormalities will result in reduced myocardial relaxation velocities. Doppler tissue imaging is a novel noninvasive imaging modality that is capable of quantifying myocardial tissue velocities and may therefore be useful to identify allograft rejection. METHODS: In this observational study, 121 heart transplant recipients underwent pulsed-wave Doppler tissue imaging at the time of their surveillance endomyocardial biopsies. Peak relaxation and systolic velocities were measured from the inferior wall blinded to clinical biopsy. Biopsy results were classified as rejecting (3a, 3b, 4) or nonrejecting (0, 1a, 1b). RESULTS: The peak relaxation velocity in nonrejecting allograft recipients (n = 98) was 0.21 m/sec +/- 0.01. During moderate allograft rejection (n = 16), peak relaxation velocities decreased to 0.14 m/sec +/- 0.01 (p < 0.0001), and subsequently increased to 0.23 m/sec +/- 0.0 after successful treatment (p = 0.0001). Peak systolic velocities did not change during rejection, 0.08 m/sec +/- 0.02 when compared with nonrejecting recipients 0.09 +/- 0.02 (p = NS). With a cutoff value of less than 0.16 m/sec, the sensitivity of peak myocardial relaxation velocities for detection of rejection was 76%. The specificity and negative predictive values were 88% and 92%, respectively. CONCLUSION: Moderate allograft rejection results in reduced myocardial relaxation velocities, which can be detected noninvasively with pulsed-wave Doppler tissue imaging. Hence, Doppler tissue imaging is a useful noninvasive tool to exclude allograft rejection.     

Microsatellite polymorphism in Anopheles maculatus, a malaria vector in Thailand

Between January 1993 and February 1993, the left internal thoracic arteries of 40 consecutive patients scheduled for aortocoronary bypass operation were examined by transthoracic B-mode imaging. Perioperative measurements correlated well with preoperative noninvasive measurements (r = 0.914). In the postoperative period, B-mode images could not be obtained in 17 (44.7%) of 38 patients. Adequate Doppler spectra of the internal thoracic artery were obtained in all patients preoperatively and in 36 (94.7%) of 38 patients postoperatively. Preoperatively a triphasic wave form was obtained with a large systolic peak followed by small reversed and diastolic components in all patients. Postoperatively this triphasic wave form had been converted into a combined systolic-diastolic wave form. In all patients peak systolic velocity of the internal thoracic artery decreased (96.4 +/- 15.3 vs 64.2 +/- 18.9 cm/sec., P < 0.05), and peak diastolic velocity increased (21.7 +/- 8.8 vs 28.3 +/- 11.2 cm/sec., P < 0.05) significantly in the postoperative period as compared with the preoperative values. A slight decrease in peak systolic and diastolic velocities was detected at twelve months postoperatively. This study indicates that transthoracic B-mode imaging and Doppler spectrum analysis are reliable techniques in the preoperative and postoperative assessment of the internal thoracic artery in myocardial revascularization.     

Color-coded measures of myocardial velocity throughout the cardiac cycle by tissue Doppler imaging to quantify regional left ventricular function

TDI is a new echocardiographic technique that calculates and displays color-coded myocardial velocity on-line. To determine the feasibility of endocardial velocity throughout the cardiac cycle as a means to quantify regional function, 20 normal subjects aged 30 +/- 5 years and 12 patients with heart disease aged 62 +/- 17 years were studied with a prototype TDI system. TDI M-mode images were acquired by using a multicolored velocity map (display range, -30 to 30 mm/sec; temporal resolution, 90 Hz). Color-coded velocity data were then converted to numeric values off-line at 50 msec intervals. Posterior wall velocities throughout the cardiac cycle by TDI were closely correlated with velocity calculations from the first derivative of routine digitized M-mode tracings (group mean r = 0.88 +/- 0.03, SEE = 7.0 +/- 1.1 mm/sec). Anteroseptal TDI color-coded systolic velocity occurred 164 +/- 84 msec from the onset of the electrocardiographic QRS compared with 203 +/- 33 msec in the posterior wall (P < 0.05) in normal subjects, consistent with normal electrical activation. Significant differences in systolic and diastolic posterior wall TDI velocity data were observed in patients with hypokinetic or akinetic segments assessed by independent routine study when compared with normal controls. Calculated systolic and early diastolic posterior wall TDI indexes correlated significantly with percentage of wall thickening. Of abnormal anteroseptal segments, TDI systolic time velocity integrals were significantly different than normal and correlated with percentage of wall thickening. TDI has potential to quantitatively assess regional left ventricular function.     

Cardiomyoplasty: hemodynamic benefit to normal and depressed canine left ventricular function

This study examined the effects of cardiomyoplasty with vascular delay on canine normal and depressed left ventricular (LV) function. To improve viability of the latissimus dorsi muscle (LDM), vascular delay was performed 2 weeks before cardiomyoplasty in 10 mongrel dogs. Two weeks after cardiomyoplasty, LV function was evaluated by simultaneously measuring LV and aortic pressure, and aortic flow. The LDM was stimulated at a ratio of 1:4-1:7 synchronously with ventricular systole. Microspheres (90 mu) were sequentially injected into the left coronary artery to depress LV function. Data were acquired and analyzed on a beat to beat basis. Results were as follows: LDM stimulation significantly augmented LV systolic pressure (LVSP) from 138 +/- 2 to 161 +/- 2* mmHg, the peak rate of change of LV pressure (+dP/dt) from 1888 +/- 46 to 2584 +/- 43* mmHg/sec, aortic systolic pressure (AoSP) from 140 +/- 2 to 159 +/- 2* mmHg, stroke volume (SV) from 11.2 +/- 0.3 to 13.3 +/- 0.3* ml, stroke work (SW) from 19 +/- 1 to 26 +/- 1* gm.m, peak aortic flow (P Qa) from 5542 +/- 142 to 7190 +/- 161* ml/min, and decreased -dP/dt from -1683 +/- 31 to -1689 +/- 49* mmHg/sec (* = p < 0.05). Microsphere injections depressed LV function, but did not affect the magnitude of the net changes between stimulated and nonstimulated beats. However, the percent changes significantly increased. Preconditioning of LDM with vascular delay augments cardiac function in LDM assisted beats. This improved performance was present in both normal as well as depressed LV function groups. Thus, investigations of cardiomyoplasty may not necessarily require a model of severe myocardial dysfunction. Vascular delay offers an important preconditioning method of LDM to augment cardiac function in cardiomyoplasty.     

Inotropic reserve and histological appearance of hibernating myocardium in conscious pigs with ameroid-induced coronary stenosis

Inotropic reserve, demonstrated with administration of sympathomimetic amines, is characteristic of hibernating myocardium. The goal of this study was to determine whether inotropic reserve was present following chronic coronary artery constriction in the pig, which is one potential model of hibernating myocardium. The effects of isoproterenol were examined in five conscious pigs 21 +/- 2.1 days after ameroid implantation on the left circumflex coronary artery on measurements of left ventricular (LV) pressure, LV dP/dt, and regional wall thickening in the ameroid-dependent zone (posterior wall) and contralateral non-ischemic zone (anterior wall). Isoproterenol, 0.1 microgram/kg/min, increased LV dP/dt by 96 +/- 11%, heart rate by 43 +/- 13 beats/min, and normalized systolic wall thickening, slightly, but not significantly more in the ameroid-dependent zone (+1.57 +/- 0.31 mm) than in the contralateral non-ischemic zone (+1.04 +/- 0.31 mm), although the baseline wall thickening was reduced significantly in the ameroid-dependent zone. This occurred at a time when baseline myocardial blood flow was preserved and myocardial perfusion in the ameroid-dependent zone was derived in part from the native coronary circulation and also through collateral channels. Two weeks later histological evidence of lesions characteristic of hibernating myocardium, i.e., myofibrolysis and increased glycogen deposition, were observed. Thus, these histological changes and the confluence of chronically depressed regional function and residual inotropic reserve in the conscious pig with chronic ameroid-induced coronary constriction support this model for further study of hibernating myocardium.     

Diastolic dysfunction in patients with chronic kidney failure on a hemodialysis program

OBJECTIVE: The aim of this study was to analyse different ultrasound parameters for the assessment of isolated left ventricular diastolic dysfunction (LVDD) in patients with chronic renal failure (CRF) on periodic hemodialysis (HD), comparing pulsed wave Doppler with pulsed tissue Doppler. MATERIALS AND METHODS: Forty-seven patients with CRF on HD (61% were male; mean age was 51.0 +/- 16.5 years, mean HD time--3.7 +/- 3.8 years, 38% had hypertension, 17% had diabetes) were studied by echocardiography (bidimensional, M-Mode, flow pulsed Doppler and tissue Doppler imaging). All patients had symptoms of left heart failure-class II NYHA, were in sinus rhythm and had no symptoms of ischemic heart disease. The presence of abnormal LV regional contractility was the exclusion criteria. According to their mitral inflow profile Doppler characteristics, patients were included in two groups: Group A (E/A > 1; n = 21) and B (E/A < 1; n = 26). We compared: LV dimensions and function, left atrial (LA) dimension. Gaasch index, LV mass index. E and A wave velocities (in flow pulsatile Doppler and tissue Doppler). E/N ratio in tissue Doppler, isovolumetric relaxation time (IVRT) and deceleration time (DT). RESULTS: There were no significant differences in the prevalence of age > or = 65 years male sex, hypertension or diabetes between group A and B patients, and almost all patients were on hemodialytic treatment for more than one year (81% vs 85%: NS). LV hypertrophy was present in almost all group A and B patients (A--95% vs B--85.5%; NS). Group A, compared with group B, had a difference in the Gaasch index (2.45 +/- 0.3 vs 2.08 +/- 0.4; p < 0.05), E wave velocity in flow pulsatile Doppler and tissue Doppler (cm/sec) (110 +/- 27 vs 62 +/- 20; p < 0.001 and 41 +/- 15 vs 28.5 +/- 16; p < 0.05), E/A ratio in tissue Doppler (1.3 +/- 0.4 vs 0.8 +/- 0.3; p < 0.001). IVRT (msec) (80.7 +/- 15.2 vs 113.5 +/- 28.3; p < 0.001) and DT (msec) (189.7 +/- 24 vs 278.2 +/- 17.9; p < 0.001). According to the E'/A' ratio in tissue Doppler, group A patients were divided in another two groups: E'/A' > 1 (13/21--62%) and < 1 (8/21--38%) and a significantly longer IVRT (75.8 +/- 9.3 vs 100.9 +/- 3.2; p < 0.001) and DT (178 +/- 15 vs 240 +/- 20; p < 0.001) and a greater LA dimension (37.6 +/- 6.9 vs 44.6 +/- 6.9; p < 0.05) were found. CONCLUSIONS: Pulsed wave Doppler is the most useful non invasive method for assessment of global diastolic dysfunction. In our study, 17% of the patients had E/A < 1 only in the tissue Doppler study. These patients probably had a pseudonormal mitral pattern.     

Effects of felodipine on left ventricular systolic and diastolic performance in congestive heart failure

We studied the effects of a dihydropyridine calcium blocker, felodipine, on left ventricular (LV) contractile performance and diastolic filling dynamics in conscious dogs with pacing-induced congestive heart failure (CHF) before and after autonomic blockade. Eleven conscious dogs were instrumented to measure micromanometer LV and left atrial (LA) pressure (P) and to determine LV volume (V) from three dimensions. CHF was induced by 4 to 5 weeks of right ventricular pacing. After CHF, the mean LV end-diastolic (ED) P increased (9.7 +/- 2.9 vs. 27.9 +/- 6.8 mm Hg, P < .05), LVEDV and end-systolic (ES) V increased and stroke volume (SV) decreased (15.3 +/- 2.4 vs. 9.6 +/- 3.0 ml, P < .05). The time constant of LV relaxation (T) (25.9 +/- 2.9 vs. 37.9 +/- 5.1 msec, P < .05) and LVES wall stress (WS) (63.4 +/- 21.0 vs. 74.6 +/- 23.7 g/cm2, P < .05) also increased. After CHF, felodipine (25 nmol/kg i.v., plasma concentrations 17.4 +/- 3.2 nmol/L) produced significant decreases in LVESP (119 +/- 12 vs. 96 +/- 11 mm Hg, P < .05), arterial elastance, total systolic resistance (TSR) (0.11 +/- 0.04 vs. 0.07 +/- 0.03 mm Hg/ml/min, P < .05) and LVESWS (74.6 +/- 23.7 vs. 60.2 +/- 17.3 g/cm2, P < .05). Felodipine increased the slopes of the ESP-V relation (5.6 +/- 1.5 vs. 7.8 +/- 0.7 mm Hg/ml, P < .05), the dP/dtmax-EDV relation (51.4 +/- 6.1 vs. 85.3 +/- 10.1 mm Hg/ml sec, P < .05) and the stroke work-EDV relation (69.8 +/- 7.1 vs. 78.9 +/- 7.1 mm Hg, P < .05) and shifted all three relations to the left, indicating enhanced contractile performance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Educating patients about the benefits and drawbacks of hormone replacement therapy

Transthoracic Doppler echocardiography was used to evaluate the technique of measuring and normal patterns of pulmonary venous flow in fourteen normal dogs. Polyphasic pulmonary venous flow profiles were obtained in all dogs, consisting of one (S) or two (SE and SL) systolic forward flow waves, one early diastolic forward flow wave (D), one reverse flow wave (R) related to atrial contraction, and one reverse flow wave (R2) observed after cessation of systolic flow. Pulmonary venous flow was laminar in 9 dogs (65%). Maximal flow velocity during systole (0.39 +/- 0.14 m/sec) was significantly lower (P < 0.01) than in early diastole (0.56 +/- 0.14 m/sec). During late diastole peak flow velocity was 0.20 +/- 0.08 m/sec and maximum R2 velocity was 0.17 +/- 0.05 m/sec. Duration of mitral A-wave was significantly greater (P < 0.05) than R-wave duration in all dogs (0.075 +/- 0.010 vs 0.058 +/- 0.012 sec). These results can be used for comparison with patterns found in disease states.     

Inhibition of neuronal nitric oxide synthase by antipsychotic drugs

Hydralazine was administered at cardiac catheterization to eight children with a ventricular septal defect (age: 2.2-8.8 years), and the extent of afterload reduction was determined using aortic input impedance and wall stress. The pulmonary to systemic blood flow ratio decreased from 2.2 +/- 0.8 to 1.8 +/- 0.4 (p < 0.05) and the pulmonary systemic resistance ratio increased from 0.11 +/- 0.08 to 0.13 +/- 0.10 (p < 0.05) after hydralazine administration. Hydralazine reduced mean aortic pressure and the amplitude of the late systolic peak of the aortic pressure wave. Peak flow velocity in the descending aorta increased from 62 +/- 14 to 81 +/- 24 cm/sec (p < 0.05). Peripheral resistance decreased significantly from 13.3 +/- 5.9 to 6.6 +/- 3.7 10(3) dyn sec/cm3 (p < 0.05). The modulus of the first harmonic, indicating pulse wave reflection, decreased from 1196 +/- 575 to 815 +/- 382 dyn sec/cm3 (p < 0.05). The characteristic impedance, indicating aortic stiffness, did not change. End-systolic wall stress decreased significantly from 54.4 +/- 16.7 to 34.8 +/- 10.2 g/cm2 (p < 0.01). Hydralazine acutely achieved afterload reduction by reducing both peripheral resistance and pulse wave reflection, and increased stroke volume.     

Left ventricular function in children with the Marfan syndrome

Aortic dilatation and heart valve lesions are common in the Marfan syndrome but whether primary alterations occur in left ventricular (LV) function has not been studied hitherto. LV size, mass and systolic as well as diastolic function were studied by M-mode and Doppler echocardiography and cine magnetic resonance imaging in 22 Marfan children aged 3.0-15.4 years and in 22 age-matched healthy children. No child had significant valve disease. Heart rate and systolic blood pressure were comparable in the groups but diastolic blood pressure was higher in the controls (67 +/- 7 mmHg vs 62 +/- 8 mmHg, P = 0.030). No statistically significant differences were found in LV size, mass or systolic function. The Marfan children had slower LV peak diameter lengthening rates (106 +/- 27 mm.s-1 vs 132 +/- 29 mm.s-1, P = 0.004), prolonged relaxation times (155 +/- 22 ms vs 140 +/- 19 ms, P = 0.023), slower deceleration of the early transmitral velocity (580 +/- 144 cm.s-1 vs 720 +/- 160 cm.s-2, P = 0.006), and smaller early-to-late peak velocity ratios (1.99 +/- 0.40 vs 2.29 +/- 0.46, P = 0.031). These data indicate that LV early diastolic function (relaxation) is impaired in the Marfan syndrome. Weakened elastic recoil due to the underlying connective tissue abnormality may best explain this novel observation.     

Reversibility of changes in left and right ventricular geometry and hemodynamics in pulmonary hypertension. Echocardiographic characteristics before and after pulmonary thromboendarterectomy

Pulmonary thromboendarterectomy (PTE) leads to an acute decrease of right ventricular (RV) afterload in patients with chronic thromboembolic pulmonary hypertension. We investigated the changes in right and left ventricular (LV) geometry and hemodynamics by means of transthoracic echocardiography. The prospective study was performed in 14 patients (8 female, 6 male; age 55 +/- 20 years) before and 18 +/- 12 days after PTE. Total pulmonary vascular resistance and systolic pulmonary artery pressure were significantly decreased (PVR: preoperative 986 +/- 318, postoperative 323 +/- 280 dyn x s/cm5, p < 0.05; PAP preoperative 71 +/- 40, postoperative 41 +/- 40 mm Hg + right atrial pressure, p < 0.05). End diastolic and end systolic RV area decreased from 33 +/- 12 to 23 +/- 8 cm2, respectively, from 26 +/- 10 to 16 +/- 6 cm2, p < 0.05. There was an increase in systolic RV fractional area change from 20 +/- 12 to 30 +/- 16%, p < 0.05. RV systolic pressure rise remained unchanged (516 +/- 166 vs. 556 +/- 128 mm Hg/sec). LV ejection fraction remained within normal ranges (64 +/- 16 vs. 62 +/- 12%). Echocardiographically determined cardiac index increased from 2.8 +/- 0.74 to 4.1 +/- 1.74 l/min/m2. A decrease in LV excentricity indices (end diastolic: 1.9 +/- 1 vs. 1.1 +/- 0.3, end systolic: 1.7 +/- 0.6 vs. 1.1 +/- 0.4, p < 0.05) proved a normalization of preoperatively altered septum motion. LV diastolic filling returned to normal limits: (E/A ratio: 0.62 +/- 0.34 vs. 1.3 +/- 0.8; p < 0.05); Peak E velocity: 0.51 +/- 0.34 vs. 0.88 +/- 0.28 m/sec, p < 0.05; Peak A velocity: 0.81 +/- 0.36 vs. 0.72 +/- 0.42 m/sec, ns; E deceleration velocity: 299 +/- 328 vs. 582 +/- 294 cm/sec2, p < 0.05; Isovolumic relaxation time: 134 +/- 40 vs. 83 +/- 38 m/sec, p < 0.05). We could show a marked decrease in RV afterload shortly after PTE with a profound recovery of right ventricular systolic function--even in case of severe pulmonary hypertension. A decrease in paradoxic motion of the interventricular septum and normalization of LV diastolic filling pattern resulted in a significant increase of cardiac index.     

Cardiac muscarinic receptor function in rats with cirrhotic cardiomyopathy

The pathogenesis of cirrhotic cardiomyopathy remains unclear. Because ventricular contractility is dependent on the interplay of stimulatory beta-adrenergic and inhibitory muscarinic receptors, we aimed to examine a possible role of muscarinic M2 receptor overactivity in a rat model of cirrhotic cardiomyopathy. Cirrhosis was induced by bile duct ligation (BDL), while controls underwent sham operations. Contractile responses to the muscarinic agonist carbachol were measured in situ in the autonomic-denervated pithed rat and in vitro in isolated ventricular papillary muscles. Ventricular sarcolemmal plasma membranes were isolated by sucrose density gradients, and muscarinic receptor characteristics were studied using 1-[N-methyl-3H]scopolamine (NMS). Membrane adenylyl cyclase activity was tested by a protein binding assay. Maximum first time derivative of peak ventricular systolic pressure (+dP/dt) for sham-operated and cirrhotic rats at baseline was 3,599 +/- 296 versus 1,226 +/- 63 mm Hg/sec (P < .01). Maximum first time derivative of ventricular diastolic relaxation (-dP/dt) for sham and cirrhotic rats at basal levels was -3,040 +/- 235 versus -864 +/- 59 (P < .01). The +dP/dt(max), and -dP/dt(max) responses to carbachol were blunted in the cirrhotic rats. The cirrhotic papillary muscles showed significantly less inhibition to incremental doses of carbachol than control rat muscles. Likewise, isoproterenol-stimulated membrane adenylyl cyclase activity was significantly less inhibited by carbachol doses in the cirrhotic rats. Membrane M2 receptor density and binding affinity in cirrhotic rat hearts were similar to controls. We conclude that muscarinic responsiveness was blunted in cirrhotic hearts, but this was not caused by receptor down-regulation, suggesting changes in postreceptor factors. These changes in muscarinic function are likely compensatory, and M2 receptor overactivity is not involved in the genesis of cirrhotic cardiomyopathy.     

Influence of one bout of intensive running on lymphocyte micronucleus frequencies in endurance-trained and untrained men

This clinical investigation was designed to determine the effect of changes in loading patterns on left ventricular (LV) relaxation when heart rate was maintained constant. Not only were changes noted in total load or time in which load is changed, but also the contour of the ascending aortic systolic pressure wave. Twenty patients were studied. LV and ascending aortic pressure were measured by a multisensor catheter under baseline conditions (C) and after an intravenous injection of 2.5 microg angiotensin (A) and sublingual administration of 0.3 mg nitroglycerin (N). A bipolar pacing catheter was placed in the right atrium to maintain a constant heart rate throughout the protocol. The augmentation index (AI), which characterizes the contour of the ascending aortic systolic pressure wave, was defined as the ratio of the height of the late systolic shoulder/peak to that of the early systolic shoulder/peak in the pulse. The rate of isovolumic LV pressure decline was calculated as a time constant (Tau). Ascending aortic systolic pressures (mmHg) were 127+/-29 (C), 158+/-20 (A) and 109+/-15 (N). AI were 1.61+/-1.14 (C), 2.08+/-1.11 (A) and 1.27+/-1.14 (N). Tau values (msec) were 49+/-4 (C), 54+/-4 (A) and 45+/-5 (N). Tau was prolonged proportionally with increasing AI (p<0.001, r=0.64). It was concluded that late systolic pressure augmentation in the ascending aorta is one important factor that influences the rate of isovolumic left ventricular pressure decline in humans.     

An investigation of ethnic and gender differences in the pharmacodynamics of haloperidol

To observe pulmonary venous flow in dogs, the echocardiographic imaging planes and the techniques for examination, and the validations of anatomic location were investigated. Then, the velocity pattern of pulmonary venous flow was recorded in normal conscious dogs. Six imaging planes were available for observing the right or left caudal lobe pulmonary venous flow with two-dimensional or pulsed Doppler echocardiography. Of these, the left lateral apical 4-chamber view can be applied as standard view, because the pulmonary venous flow and transmitral flow could be recorded in this view simultaneously with small sampling angle. The velocity pattern of pulmonary venous flow demonstrated two forward waves in 19 of 20 dogs examined, with one peak occurring during ventricular systole and another during ventricular diastole. A reversed flow during atrial contraction was also seen in 11 dogs. In the two forward waves, the mean peak velocity and velocity-time integral of ventricular diastolic forward flow were significantly higher than those of systolic forward flow (46.49 +/- 6.79 vs. 31.13 +/- 4.92 cm/s, p < 0.0001 and 8.18 +/- 1.84 vs. 5.14 +/- 0.82 cm, p < 0.0001, respectively). The deceleration time of diastolic forward flow shortened with the increase of heart rate (r = -0.87, p < 0.0001). Pulmonary venous flow in dogs can be observed under transthoracic two-dimensional or pulsed Doppler echocardiography.     

Short deceleration time of mitral inflow E velocity: prognostic implication with atrial fibrillation versus sinus rhythm

The present study retrospectively identified 367 patients who had restrictive physiology as defined by deceleration time < or = 130 msec; 293 were in sinus rhythm (SR) (194 men and 99 women; mean age 64 +/- 14 years) and 74 were in atrial fibrillation (AF) (51 men and 23 women; mean age 72 +/- 11 years; p < 0.001). Both groups had similar underlying diagnoses and no significant difference in Doppler indices (E wave, 96 +/- 23 vs 99 +/- 22 cm/sec in SR and AF, respectively; deceleration time, 116 +/- 12 vs 116 +/- 13 msec; and left ventricular outflow tract time velocity integral, 14.8 +/- 4.8 vs 14.5 +/- 4.4 cm). Left ventricular ejection fraction was significantly lower in SR patients (29% +/- 16% vs 39% +/- 20%; p = 0.0003). There were 120 deaths (41%) in the SR group and 35 (47%) in the AF group (median follow-up for both groups, 2.2 years). Restrictive physiology as defined by Doppler echocardiography (deceleration time < or = 130 msec) appears to predict a similar poor prognosis with AF as with SR.