Evaluation of cardiac structures and function in small experimental animals: Transthoracic, transesophageal, and intraventricular echocardiography to assess contractile function in rat heart

Objectives The efficacy of three different echocardiographic techniques to assess cardiac structures and function in the rat heart was studied. Background With increasing costs for large animal studies there is need for improved assessment of ventricular function in small animal models. Methods Transthoracic, transesophageal, or intracavitary echocardiography was performed in 138 rats using either a pediatric or an intravascular ultrasound transducer in control, infarcted, and obese rats. Left ventricular dimensions and wall thickness were measured. Results Transthoracic echocardiography allows qualitative and quantitative estimation of cardiac dimensions and ventricular function. End-diastolic and end-systolic diameters were 0.53±0.08 and 0.26±0.05 cm in controls, 0.63±0.08 and 0.41±0.07 cm in infarcted (p<0.001 vs controls), and 0.66±0.1 and 0.21±0.07 cm in obese rats (p<0.01 vs controls). Fractional shortening was 52±6% in controls, 36±5% in infarcted (p<0.001), and 68±9% in obese rats (p<0.001). Wall thickness was increased in obese rats. Transesophageal echocardiography allows a qualitative rather than quantitative assessment. Intracavitary ultrasound enabled visualization of the endocardium. Following coronary occlusion, fractional shortening and ejection fraction were decreased (30.8±4.5 vs 44.4±4.7%, p<0.005, and 46.7±8.5 vs 63.4±5.4%, p<0.005, respectively). Conclusions Transthoracic echocardiography is a non-invasive technique to sufficiently provide information about cardiac structures and function, while transesophageal echocardiography allows rather a qualitative estimation of the rat heart. Intracavitary ultrasound can be used to assess the endocardium, ventricular function, and dimensions in open-chest studies in rats. Received: 3 June 1998, Accepted: 17 July 1998     

Increased plasma apolipoprotein B levels and blood hyperviscosity in non-insulin-dependent diabetic patients: Role in the occurrence of arterial hypertension

Summary An association between arterial blood pressure and blood viscosity has been suggested in healthy and in diabetic subjects, and that the hemorheological pattern may be influenced by blood lipid alterations. In diabetic patients a relationship between arterial hypertension and blood lipid changes may therefore be suggested. This study concerns 19 type II diabetics with hyperlipidemia (triglycerides=3.2±1 mmol/l; total cholesterol=6.1±1.2 mmol/l; HDL-cholesterol=0.92±0.27 mmol/l; VLDL=29±5%) (group A), and 19 normolipidemic type II diabetics (triglycerides=1.15±0.5 mmol/l; total cholesterol=5.1±1 mmol/l; HDL-cholesterol =1.25±0.38 mmol/l; VLDL=20±5%) (group B). No differences concerning age, body weight, duration of diabetes and glycemic control were found in hyperlipidemic compared to normolipidemic diabetics. On the contrary, higher systolic and diastolic blood pressure levels were demonstrated in group A (167±14 mmHg and 101±5.2 mmHg, respectively) than in group B (144±15 mmHg, p<0.001 and 87±6.9 mmHg, p<0.001, respectively). An increase of plasma apolipoprotein B level (163±27 mg/dlvs 102±21 mg/dl, p<0.001), of plasma viscosity (1.81±0.08 mPasvs 1.51±0.07 mPas, p<0.001) and of blood viscosity (5.37±0.33 mPasvs 5.07±0.04 mPas, p<0.01, at shear-rate of 90 s⁻¹; 18.4±1 mPasvs 14.1±0.9 mPas, p<0.001 at shear-rate of 2.25 s⁻¹) was found in group A, compared to group B. Moreover several positive correlations (p<0.001) between apolipoprotein B level, plasma and blood viscosity were demonstrated in the hyperlipidemic diabetic patients. These findings suggest that blood changes in diabetes might be involved in the occurrence of blood pressure alterations. This study was presented in part at the 22nd Meeting of the European Association for the Study of Diabetes (EASD), Rome September 16–20, 1986.     

Ambulatory blood pressure monitoring in diabetic males: A method for detecting blood pressure elevations undisclosed by conventional methods

Twenty-one diabetic males, ages 20 to 61 years (mean 48.4±10.5) and 14 healthy males, 22 to 59 years (mean 42.5±10.4) consented to participate in a study during which 24-h recordings of systolic and diastolic blood pressures, heart rates, and rhythm were obtained. The diabetic subjects were considered nor-motensive except for two patients, who had been observed to have rare insignificant elevations in blood pressure and were untreated. Diabetic subjects had a higher mean maximal systolic blood pressure (160.7±49.8 mmHg) than the normal controls (132.4±12.1 mmHg) (p<0.05). They also had a higher frequency (15.1%) of systolic blood pressure readings ≥ 150 mmHg compared to normal men (0.2%) (p<0.01). The frequency of diastolic blood pressure readings ≥90 mmHg was 22.1% in the former and 9.2% in the latter group (p<0.01). Of 21 diabetic males, 14 (66.7%) had systolic pressures ≥ 150 mmHg, diastolic pressures ≥100 mmHg, or both. In the normal men, 3 (21.4%) of the 14 had such pressures. Twenty-four hour monitoring of ambulatory blood pressures revealed elevations not detected by routine casual readings in patients with diabetes.     

High-rate cardiac pacing increases blood pressure and decreases right atrial pressure in patients with hemodynamic significant acute right ventricular myocardial infarction and bradyarrhythmia

Background: In an 84-year-old patient with acute right ventricular myocardial infarction (RVI), complete heart block, and low cardiac output, a significant increase in blood pressure (BP) and decrease in right atrial pressure (RAP) were accidentally observed during the performance of high-rate ventricular pacing. Methods: Based on that observation, the acute effects of high-rate cardiac pacing (VVI or AAI) on BP and RAP were studied in 15 consecutive patients (67.4 ± 7.7 years), with hemodynamically significant RVI. Ten had advanced heart block and five had sinus bradycardia. Cardiac pacing with simultaneous recording of BP and RAP at intrinsic rhythm and at heart rates of 70,90,110,130 beats/min was performed. Results: Systolic BP (SBP) increased significantly from 94.6 ± 15 mmHg during intrinsic rhythm to 101.9 ± 13.8 mmHg-127 ± 12.2 mmHg at heart rates 70–130 beats/min (p<0.0001). Diastolic BP (DBP) also increased from 48.2 ± 8.7 to 53.9 ± 3.7–69.1 ± 3 mmHg at heart rates 70–130 beats/min, (p<0.014–0.0001). Mean RAP decreased from 14.5 ± 5 to 14.1 ± 5 mmHg-11.1 ± 4.1 mmHg at heart rates 70–130 beats/min (p = 0.16–0.0001). Significant elevation of SBP (p<0.007), DBP (p<0.0075), and decrease of RAP (p<0.038) were also detected by comparing the usual pacing rate at 70 beats/min with pacing rates at 90–130 beats/min. Conclusions: These findings, if demonstrated over a prolonged period during the acute state of RVI, may influence the management of patients with RVI to include high-rate cardiac pacing, probably in the range of 80–110 beats/min.     

Use of intra-aortic nitroglycerin in the cardiac catheterization laboratory

The purpose of this study was to determine whether nitroglycerin (NTG) injected into the ascending aorta or left ventricle would safely and effectively lower blood pressure in hypertensive patients undergoing cardiac catheterization. Fifty bolus injections of 297 ± 67 μg (mean ± SD) NTG were given to patients with a systolic blood pressure (SBP) of ?140 mm Hg (mean SBP 188 ± 20.1 mm Hg). An average drop in systolic blood pressure of 36 ± 16 mmHg (P < 0.001), diastolic blood pressure of 19 ± 7 mm Hg (P < 0.001), and left ventricular end-diastolic pressure of 4.7 ± 4 mm Hg (P = 0.001) was well tolerated in each patient. The mean time to response was 11 ± 3 sec. Intra-aortic injection of NTG is a safe and effective means to treat hypertensive patients in the cardiac catheterization laboratory. © 1995 Wiley-Liss, Inc.     

Effects of Quinapril Hydrochloride in Patients with Essential Hypertension and Impaired Renal Function

The short-term effects of administration of an angiotensin-converting enzyme (ACE) inhibitor, quinapril hydrochloride (quinapril) (5–10mg/day), for 12 weeks on blood pressure and renal function were evaluated in 8 patients (60.5±7.3 years old, mean±SD) with mild to moderate essential hypertension and mild impairment of renal function due to nephrosclerosis. Systolic blood pressure and diastolic blood pressure were significantly reduced from 163.0± 4.0 to 132.3± 17.6 mmHg (p<0.01) and from 98.3± 4.6 to 81.5± 6.4 mmHg (p<0.001), respectively, before to after treatment. Both renal plasma flow (RPF) and glomerular filtration rate (GFR) were significantly increased in all patients, from 203.9 ± 33.3 to 245.4 ± 36.7 ml/min/1.73m² (p<0.01), and from 43.4± 6.4 to 53.5± 4.6 ml/min/1.73m² (p<0.05), respectively.

Short-term quinapril administration was beneficial to renal function in patients with essential hypertension and impaired renal function.     

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Summary Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. ’Up BRS' sequences–increases in systolic blood pressure associated with lengthening of R-R interval, and ’down BRS' sequences–decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. ’Up BRS' when supine was 11.2 ± 1.5 ms/mmHg (mean ± SEM) compared with 20.4 ± 1.95 in control subjects (p < 0.003) and when standing was 4.1 ± 1.9 vs 7.6 ± 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 ± 1.2 vs 22 ± 2.6 (p < 0.001) and standing was 4.4 ± 1.9 vs 7.3 ± 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05–0.15 Hz as low-frequency and 0.2–0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 ± 62.8 vs 746.6 ± 77.6 ms² p = 0.002) and high frequency bands 125.2 ± 12.9 vs 459.3 ± 89.8 ms² p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 ± 0.53 vs 4.6 ± 0.55, p < 0.002 supine: 3.8 ± 0.49 vs 6.6 ± 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients. [Diabetologia (1996) 39: 1385–1391] Received: 9 April 1996 and in revised form: 19 July 1996     

Mechanism of left a trial enlargement related to ventricular diastolic impairment in hypertension

Background and hypothesis: Systemic hypertension is the leading cause of left ventricular (LV) hypertrophy. The present study aimed to investigate the mechanism of left atrial (LA) enlargement in patients with hypertensive heart disease during cardiac catheterization. Methods: Data were obtained from eight control subjects and seven patients with hypertensive heart disease. Left atrial and LV pressures from catheter-tip micromanometer, and LA and LV volumes from biplane cineangiograms were analyzed during the same cardiac cycle. Results: Left atrial maximal volume were 93 ± 26 ml in patients with hypertensive heart disease and 63 ± 12 ml in control subjects (p<0.05). In patients with hypertensive heart disease, time constant of LV relaxation was significantly greater than that in controls (54 ± 18 vs. 31 ± 16 ms, respectively p<0.01). Left atrial maximal volume correlated with time constant of LV relaxation (r = 0.86, p<0.01). The ratio of LV filling volume before LA contraction to LV stroke volume in patients with hypertensive heart disease was significantly lower than that in control subjects (65 ± 13 vs. 76 ± 7%, respectively p<0.05). On the other hand, the ratio of LV filling volume during LA contraction to stroke volume in patients with hypertensive heart disease was significantly higher than that in controls (35 ± 13 vs. 24± 7%, respectively p<0.05). Left atrial volume before LA contraction in patients with hypertensive heart disease was significantly larger than that in controls (74 ± 22 vs. 47 ± 10 ml, respectively, p<0.01). During LA contraction, LA work was significantly increased in patients with hypertensive heart disease compared with that in controls (274 ± 101 vs. 94 ± 42 mmHg. ml, respectively p<0.001). Left atrial work showed significant correlation with LA volume before LA contraction (r = 0.75, p <0.01). Conclusion: Left ventricular diastolic filling was impaired in patients with hypertensive heart disease. Enlargement of left atrium might be attributed to the impairment of blood flow from left atrium to left ventricle due to the increased LV stiffness.     

Reversal of left ventricular hypertrophy with captopril: Heterogeneity of response among hypertensive patients

Reversal of left ventricular hypertrophy (LVH) has been reported not to occur with all antihypertensive agents. Moreover, a dissociation between blood pressure response to medical therapy and reversal of ventricular hypertrophy has been previously observed. To evaluate the effects of captopril we studied the electrocardiographic (ECG) changes in 26 severe hypertensive patients who received the drug for more than one year. In 14 patients with normal pretreatment ECG, captopril controlled blood pressure effectively [132±2.9 (SE) to 104±3.9 mmHg, p<0.001], but had no effect on ECG voltage. In 12 patients with pretreatment LVH, two different response patterns were observed despite similar blood pressure control (144±4.9 to 102±3.1 mmHg and 148±7.3 to 109±7.3 mmHg, p<0.001 for both): seven had complete normalization of ECG while five had residual LVH pattern. No significant difference was found between the latter two groups in regard to age, sex, weight, etiology of hypertension, pretreatment ECG voltage, blood pressure, plasma renin activity, duration of treatment and duration of maintained blood pressure control. The reversal of LVH pattern occurred early (between 12 to 16 months) with no overall correlation between lowering of blood pressure and ECG voltage changes. The heterogeneity of response observed in this study suggests that factors other than blood pressure control modify the reversal of cardiac hypertrophy by antihypertensive therapy.     

Evidence for transient limitations in coronary blood flow during unstable angina pectoris: hemodynamic changes with spontaneous pain at rest versus exercise-induced ischemia following stabilization of angina

The pathophysiologic basis for the deterioration of patients with stable angina pectoris to unstable angina is unclear. Central to this issue is the question of whether myocardial ischemia occurs at the same or at a lower myocardial oxygen demand during unstable periods as during stable periods. Consequently, we compared myocardial oxygen demand in 12 patients at the onset of spontaneous pain during unstable angina to myocardial oxygen demand during exercise-induced ischemia after resumption of stable angina, 6–12 weeks later. Myocardial oxygen demand was estimated from values for heart rate (HR), systolic blood pressure (BP), and the rate-pressure product (RPP). Rate-pressure product is the heart rate × systolic blood pressure × 10^-2 (mmHg/min/10²). There was definite evidence for coronary artery spasm for only one patient. There was no difference in heart rate, blood pressure, or rate-pressure product during pain-free intervals in the hospital and just before the start of exercise testing. Mean H R (71.2± 11.1 beats/min; mean ± standard deviation) and RPP (95.8±20.0 mmHg/min/10²) just before spontaneous angina during the unstable period were significantly lower (p<0.001) than at the termination of bicycle ergometry in both the supine (HR, 96.9±10.5 beats/min; RPP, 141.8±25.0 mmHg/min/10²) and upright (HR, 98.1±13.6 beats/min; RPP, 143.0±32.2 mmHg/min/10²) positions. Blood pressure (134.5 ± 17.6 mmHg) just before spontaneous angina was significantly lower than at the conclusion of both supine (145.6±13.3 mmHg) and upright (145.1 ±18.6 mmHg) ergometry. The observation that myocardial oxygen demand was lower at the threshold of ischemia with spontaneous angina than with exercise-induced ischemia is consistent with the hypothesis that there were transient, reversible limitations in coronary blood flow during the period of unstable angina. There was also a moderate but significant rise in estimated myocardial oxygen demand just before spontaneous angina in these patients, but the nature of the data do not allow us to distinguish whether or not this rise was part of the cause or an effect of ischemia. While the results of this study did not identify the cause for the transient limitations in coronary flow, coronary artery spasm without ST-segment elevation, intracoronary platelet aggregates, and hemorrhage into atherosclerotic plaques are possibilities that are consistent with these hemodynamic observations.     

Mechanisms underlying air aspiration in patients undergoing left atrial catheterization

Background : Air embolism in patients undergoing percutaneous interventions requiring access to the left atrium (LA) represents a potentially fatal complication. Here we tested if a decline in LA pressures following sedation represents an important mechanistic link underlying air intrusion into the LA. Methods and Results : Left atrial pressures were measured in 26 consecutive patients (49 ± 14 years; 27% male), who underwent percutaneous atrial septal occlusion for persistent foramen ovale or secundum atrial septal defects. Patients either received sedation by propofol allowing for guidance by transesophageal echocardiography (n = 13) or underwent occluder implantation without sedation and under fluoroscopic control only (n = 13). Whereas mean exspiratory LA pressures remained unchanged in either group, sedation provoked a marked decline in the mean inspiratory LA pressure as compared to non‐sedated patients (Δp 6.9 ± 8.6 mm Hg vs. 0.1 ± 1.2 mm Hg in nonsedated patients, P < 0.001). Ex vivo experiments evaluating the air‐tightness of different sheaths in response to negative pressures revealed air aspiration at –13.4 ± 1.2 mm Hg of suction in all cases, once a guide wire was inserted. Conclusions : Negative LA pressures in conjunction with air‐leaking sheaths are identified as potentially important factors for air intrusion into the LA with the patient's sedation being a primary risk factor to lower LA pressure levels. The results advocate close monitoring of LA pressures during intervention, prevention of airway collapse and protection of LA sheaths from communication with the atmosphere, during procedures under sedation. © 2008 Wiley‐Liss, Inc.     

Effects of heart rate on flow velocity of the left atrial appendage in patients with nonvalvular atrial fibrillation

Background and hypothesis: Flow velocity of the left atrial appendage (LAA) is thought to be important in thrombus formation in association with blood stasis and the development of spontaneous echo contrast. The effects of heart rate on peak flow velocity of the LAA have not been studied in patients with nonvalvular atrial fibrillaton. Methods: Using transesophageal Doppler echocardiography, peak flow velocity of the LAA was measured at the junction between the left atrium and the LAA during left ventricular (LV) systole and diastole in 21 patients with nonvalvular atrial fibrillation. In six cases, the average peak flow velocity of the LAA for 10 consecutive beats with moderately long R-R intervals (LI beats) was compared with those for 3-5 consecutive beats with extremely short R-R intervals (SI bets). Results: Average peak flow velocity of the LAA during LV diastole was significantly higher than that during LV systole (26.5 ± 15.7 vs. 19.3 ± 10.4 cm/s, p<0.01). In SI beats, average peak flow velocity of the LAA was significantly lower than that in LI beats (17.1 ± 12.1 vs. 21.2 ± 12.9 cm/s, p<0.01). Conclusion: An increased heart rate reduced the peak flow velocity of the LAA in patients with nonvalvular atrial fibrillation, which would promote blood stasis in the LAA.     

Raised circulating plasma levels of atrial natriuretic peptide in adolescent and adult patients with cystic fibrosis and pulmonary artery hypertension

Since pulmonary artery hypertension (PH) complicates advanced stages of cystic fibrosis (CF), we wondered whether plasma concentrations of h-ANP would be increased in adult patients with CF. Furthermore, if only the right ventricle is faced with an increased afterload in these patients, the increased h-ANP plasma levels should stem primarily from the right atrium. To test this hypothesis we studied 12 adult patients with CF in a clinically stable condition using right heart catheterization. Mean pressures were measured in the right atrium (Pra) and pulmonary artery (Ppa), pulmonary capillary wedge (PCWP) position, and blood were drawn from the pulmonary artery and from a peripheral vein to determine h-ANP. Plasma levels in the pulmonary artery were significantly higher than in a peripheral vein (54.3±6.0 pg/ml vs. 32.2±4.4 pg/ml; p<0.001). Four of the 12 patients had PH (Ppa, 25.8±2.9 mmHg) whereas 8 patients exhibited normal pulmonary artery pressures (Ppa, 15.9±0.7 mmHg). Patients with PH had higher Pra (4.2±0.4 mmHg) than patients with CF without PH (1.9±0.7 mmHg; p < 0.05). Plasma h-ANP concentrations were significantly higher in patients with CF with PH (70±10.4 pg/ml in the pulmonary artery; 42.6±4 pg/ml in a peripheral vein) than in patients with normal pulmonary artery pressure (43±3.3 pg/ml in the pulmonary artery; p<0.01; 24.7±5.6 pg/ml in a peripheral vein; p<0.05). Although our results are derived from a small group of patients with CF, we conclude from our results that in patients with CF PH may cause increased h-ANP secretion. The right atrium seems to be a major source.     

Cardiovascular effects of breathing 95 percent oxygen in children with congenital heart disease

The hemodynamic effects of breathing 95% oxygen were evaluated in 26 children with congenital heart disease. Aortic, pulmonary arterial, right atrial, and pulmonary arterial wedge pressure, aortic and pulmonary artery oxygen saturation, and blood gas, cardiac index, and heart rate were measured in room air and after each patient had breathed 95 % oxygen for 10 (n = 26) and 20 (n = 5) minutes. Measurements were repeated with the patient again breathing room air for 10 (n = 11) and 20 (n = 6) minutes. After 10 minutes of 95% oxygen, arterial partial pressure of oxygen increased from 85 ± 13 to 420 ± 89 torr (p < 0.001). Aortic mean pressure increased from 80 ± 10 to 83 ± 10 mm Hg (p < 0.01), and systemic vascular resistance increased from 20 ± 7 to 26 ± 8 U (p < 0.001). The cardiac index decreased by 21 % from 3.96 ± 0.94 to 3.12 ± 0.74 liters/min/m² (p < 0.001) and the stroke index decreased by 11% (p < 0.001). A 23% decrease in oxygen consumption (p < 0.001) was observed, and oxygen transport decreased from 763 ± 179 to 600 ± 161 ml O₂/min/m² (p < 0.001). Cardiac index, stroke index, and systemic vascular resistance did not return to normal until 20 minutes after cessation of oxygen breathing. To determine whether reflex bradycardia is responsible for these oxygen-induced hemodynamic changes, heart rate was kept constant by atrial pacing in a second group of 5 patients. In these children, significant decreases in cardiac index, stroke index, and oxygen consumption, and increases in systemic vascular resistance also occurred with 95% oxygen. Thus, in children with acyanotic congenital heart disease, hyperoxia increases aortic pressure and systemic vascular resistance and decreases cardiac index, stroke index, oxygen consumption, and oxygen transport.     

Further Studies on the Hypernoradrenergic State of Treated Hypertensives: Effect of Captopril

We investigated the effect of captopril on plasma norepinephrine concentration and blood pressure in two groups of hypertensive patients. One group consisted of five severely hypertensive patients rendered hypernoradrenergic by administration of a minoxidil-propranolol-diuretic regimen. The other group was ten untreated mildly hypertensive patients.

Two hours after 12.5mg of captopril, blood pressure was lowered (p<.05) in four of the five hypernoradrenergic patients from 180±8/102±8 to 132±7/77±8 mmHg. Chronic administration of 100-150mg of captopril tid caused no further blood pressure reduction.

Precaptopril plasma norepinephrine concentration was 925±206 and two hours after the 12.5mg dose was 807±80 pg/ml. Three months later having advanced the dose to 300-450 mg/day it was lower (p<.05) at 752 pg/ml. The acute blood pressure response correlated (r=-0.72, p<.001) with the precaptopril plasma norepinephrine.

Precaptopril blood pressure in the mild hypertensive patients was 146±4/98±1, after a 25-100mg dose it was 137±6/91±2 (diastolic p<.05) and at two months with the same captopril dose bid it was 141±8/88±4 mmHg (diastolic p<.01). Corresponding initial PNE was 425±72, two hours after captopril 405±47 and 310±63 pg/ml (p<.05) with chronic administration.

Thus, captopril lowers blood pressure in both hypernoradrenergic and eunoradrenergic hypertensive patients without increasing plasma norepinephrine suggesting some unique dampening effect of this drug on the sympathetic nervous system. Also, addition of captopril to triple therapy lowered blood pressure in proportion to plasma norepinephrine levels suggesting importance to its action on this sympathetic nervous system effector.     

Retrograde atrial kick in acute aortic regurgitation. study of mitral and pulmonary venous flow velocities by transthoracic and transesophageal echocardiography

Background and hypothesis: The purpose of this study was the comprehensive evaluation of the changes in pulmonary venous and mitral flow velocities of patients with acute and chronic severe aortic regurgitation. Transmitral flow velocities obtained with pulsed-wave Doppler echocardiography have been used to provide information on left ventricular (LV) filling and diastolic function. Pulmonary venous flow tracings are an important adjunct to LV inflow pattern in assessing LV diastolic function. Methods: Fourteen patients with severe aortic regurgitation (8 chronic and 6 acute) and in sinus rhythm were examined by transthoracic and transesophageal pulsed Doppler echocardiography. Mitral and pulmonary flow velocities were recorded and compared. All patients had ejection fractions > 40%. Results: Early mitral flow peak velocity was higher in patients with acute regurgitation (p<0.001). The mitral A wave was absent in five patients with acute regurgitation. In contrast, a prominent reverse atrial pulmonary systolic wave AR was demonstrated in these patients. Peak diastolic velocity of the pulmonary venous flow was greater in patients with acute aortic regurgitation (0.76 ± 0.13) than in patients with chronic aortic regurgitation (0.40 ± 0.09) (p<0.001). Peak systolic velocity did not differ significantly between the two groups. The systolic fraction of pulmonary venous flow in patients with acute aortic regurgitation was lower (0.43 ± 0.05) than that of patients with chronic regurgitation (0.63 ± 0.1) (p<0.01). All patients with acute aortic regurgitation had an S/D ratio < 1, while those with chronic regurgitation had an S/D >1 (p< 0.001) and an E/A<1. Conclusion: Patients with severe acute aortic regurgitation showed a retrograde atrial kick (absence of transmitral A wave with prominent pulmonary AR wave). These patients had an S/D ratio < 1 (restrictive Doppler pattern). Patients with chronic aortic regurgitation exhibited a Doppler pattern of abnormal LV relaxation (E/A <1, S/D > 1).     

Factors influencing heart rate variability in patients with severe aortic valve disease

Background and hypothesis: Heart rate variability (HRV) is an accepted tool for the assessment of cardiovascular autonomic tone. There are no sufficient data concerning its application to patients with severe aortic valve disease (AVD) requiring cardiac surgery. Methods: It was the aim of this study to examine HRV and its physiologic correlates in patients with severe aortic valve disease requiring cardiac surgery. The correlates of time domain indices of HRV obtained from 24-h Holter electrocardiographic recordings were analyzed in 36 consecutive patients (23 men and 13 women, mean age 62 ± 11 years) with AVD prior to cardiac surgery (aortic stenosis: 17 patients, aortic valve regurgitation: 3 patients, combined aortic valve disease: 16 patients). Results: Low values of HRV were found in the entire study group: SDNN 96.8 ± 30.9 ms, SDNNI 39.3 ± 14.4 ms, SDANN 86 ± 28.9 ms, and RMSSD 30 ± 18.1 ms. In a univariate analysis, there was no significant correlation between the time domain measures of HRV and age, gender, medication, left ventricular ejection fraction, peak aortic pressure gradient, fraction of aortic valve regurgitation, and left ventricular mass assessed by echocardiography. Patients in advanced functional classes of heart failure [New York Heart Association (NYHA) III or IV] had significantly lower values for SDNN (83.8 ± 33.6 vs. 107.3 ± 24.7 ms; p<0.05) and SDANN (72.7 ± 29.4 vs. 96.6 ± 24.3 ms; p<0.05) than patients in NYHA class I or II. Reassessment of HRV 1 week after aortic valve replacement was performed in 17 patients and showed a significant further decrease of SDNN (102.4 ± 29.7 vs. 61.5 ± 23.5 ms; p<0.001), SDNNI (40.7 ± 13.6 vs. 23.4 ± 12.4 ms; p<0.001) and SDANN (91.8 ±29.2 vs. 54.2 ± 22.8 ms;p<0.001). Conclusion: Patients with AVD requiring cardiac surgery reveal reduced time domain indices of HRV. This observation is pronounced in patients with a progressed clinical class of heart failure, whereas hemodynamic and echocardiographic parameters seem to have no significant influence on HRV parameters in this population. In addition, there is evidence of a further reduction of HRV time domain indices 1 week after uncomplicated aortic valve replacement.     

异丙肾上腺素后平卧位血压与血管迷走性晕厥关系的研究

目的 分析异丙肾上腺素给药后受试者平卧位心率、血压变化,探究血管迷走性晕厥（VVS）的预测指标。 方法 回顾性纳入2016年10月至2017年4月就诊于河南省人民医院内科因疑诊VVS而行二阶段法异丙肾上腺素倾斜试验（IHUTT）的患者182例。分析第一阶段阳性（阳性1组）、第二阶段阳性（阳性2组）和阴性组患者各阶段平卧位的心率、收缩压、舒张压变化,用ROC分析差异最显著的指标。 结果 IHUTT中,一阶段用药后,舒张压降幅在阳性1组和2组均显著高于阴性组[ (7.6 ± 8.4 )mmHg,（5.6 ± 7.8） mmHg,（1.9± 6.9） mmHg,P<0.001);二阶段用药后,舒张压降幅在阳性2组亦显著高于阴性组[(11.8± 9.1) mmHg比（3.3± 6.3） mmHg,P<0.001]。一阶段用药后舒张压降幅的AUC为0.639(95% CI: 0.54~0.739),ROC曲线的最佳cut-off为7.5 mmHg;二阶段用药后舒张压降幅AUC为0.778(95% CI: 0.694~0.862),ROC曲线的最佳cut-off为6.5 mmHg。 结论 平卧位静脉滴注异丙肾上腺素后受舒张压显著降低,可作为VVS的有效预测指标。     

Neuropeptide Abnormalities Suggest a Dopaminergic Basis for High Blood Pressure in the Spontaneously Hypertensive Rat

The spontaneously hypertensive rat (SHR) and the stroke-prone substrain (sp-SHR) have been reported to have several abnormalities in levels of peptides both in tissue and in plasma (β- endorphin, prolactin, thyroid stimulating hormone and vasopressin) when compared to the Wistar Kyoto (WKY) normotensive control rat. As the secretion of these peptides is under dopaminergic control and the abnormalities consistently suggest under-activity of the dopaminergic control system in the brain, injections of dopamine (0.4 mg/kg) were given i.c.v. to 10 SHR, 10 renal artery stenosis hypertensive rats (LRAS) and 10 genetically hypertensive rats of the New Zealand strain (GHR). Mean blood pressure fell from 205±6(SEM) mmHg to 128±8 mmHg in the SHR (p<0.001), from 184±7 mmHg to 176±7 mmHg in the LRAS (p>0.05) and from 157±5 mmHg to 138±6 mmHg in the GHR (p<0.02). These effects were unlikely to be due to leakage of dopamine out into the periphery as i.v. dopamine (0.4 mg/kg) increased blood pressure in these animals.     

Response to upright exercise after cardiac transplantation

There is little information on the hemodynamic response to upright exercise in patients who have undergone cardiac transplantation. We compared the hemodynamic and metabolic response to upright bicycle exercise in 11 patients with heart transplants and 12 controls. Patients performed two tests—a steady-state test with a right heart catheter and a maximal incremental test. During steady-state exercise at 20% of their predicted maximum workload, patients with heart transplants had a higher (mean ± SD, p < 0.05) heart rate (108 ± 11 vs. % ± 15 beats/min), mean systemic blood pressure (116 ± 17 vs. 101 ± 11 mmHg), mean pulmonary artery pressure (29 ± 9 vs. 22 ± 3 mmHg), mean pulmonary wedge pressure (14 ± 6 vs. 9 ± 2), pulmonary (302 ± 101 vs. 220 ± 50 d-sec-cm^?5 - m²) and systemic (2049 ± 531 vs. 1459 ± 520) resistance indices, and lactate concentration (3.4 ± 1.7 vs. 1.7 ± 0.4 mmol/1), and a lower stroke index (39 ± 8 vs. 50 ± 8 ml/m²) compared with controls. Cardiac index, right atrial pressure, and mixed venous oxygen saturation were similar. During the maximal exercise test, patients with heart transplants achieved a significantly lower percentage of predicted maximum heart rate (77 ± 13 vs. 91 ± 8%), workload (70 ±25 vs. 102 ± 23%), oxygen consumption (63 ± 11 vs. 108 ± 19%), and ventilation (67 ± 18 vs. 89 ± 15%) compared with controls. Heart transplant patients also had a lower blood pressure and anaerobic threshold. We conclude that heart transplant patients have an altered hemodynamic and metabolic response to upright bicycle exercise.