Repeated vaginal administration of trimeric HIV-1 clade C gp140 induces serum and mucosal antibody responses.

Vaccine-mediated prevention of primary infection with human immunodeficiency virus (HIV) may require the sustained production of antibody at mucosal portals of entry. Here, we describe a novel approach of repeated mucosal immunization by delivering an HIV-1 envelope glycoprotein (gp) in a gel formulated for intravaginal delivery. Rabbits were immunized over one to three 19-day cycles of intravaginal dosing with soluble recombinant trimeric HIV-1 clade C gp140 administered in Carbopol gel. The formulation was well tolerated. A single immunization cycle induced immunoglobulin G (IgG) antibody detected in the serum and female genital tract, and titers were boosted on further immunization. Vaccine-induced serum antibodies neutralized the infectivity of a pseudovirus carrying a heterologous clade C envelope. Our data prove the concept that repeated exposure of the female genital tract to HIV envelope can induce mucosally detectable antibody.

Continuous ambulatory peritoneal dialysis and the heart.

OBJECTIVE: To review clinical research pertaining to continuous ambulatory peritoneal dialysis (CAPD) and the heart. DATA SOURCES: A Medline computer search was employed to identify appropriate references from 1970 - 1994. Indexing terms were: continuous ambulatory peritoneal dialysis, hemodialysis, heart or cardiac, left ventricle, coronary artery disease, and survival. English and non-English language abstracts were scrutinized. STUDY SELECTION: Forty-six studies were reviewed and utilized. Numerical data extracted are reported in this review as they were reported in the original article. RESULTS: This review provides a broad-based survey of studies pertaining to CAPD and the heart. Most of the studies relate to CAPD and left ventricular structure or function. Little information exists concerning CAPD and coronary artery disease, valvular disease, pericardial disease, and cardiac arrhythmias. Studies pertaining to patient survival on CAPD identify coronary artery disease and congestive heart failure as major risk factors, but in-depth quantification of these cardiovascular disorders is lacking in the literature. CONCLUSIONS: CAPD is capable of decreasing left ventricular (LV) volume and improving LV systolic function in patients with LV enlargement and those with LV systolic dysfunction. The effect of CAPD on left ventricular hypertrophy (LVH) and LV diastolic function is variable. CAPD produces symptomatic improvement in patients with refractory congestive heart failure, but its effect on survival in such patients is uncertain. Atherogenic lipid abnormalities occur in CAPD patients. The clinical significance of these abnormalities is uncertain. Coronary artery bypass surgery can be performed safely and effectively on CAPD patients. CAPD is not arrhythmogenic. Survival of CAPD patients is similar to that of hemodialysis patients except in elderly diabetics for whom it is slightly lower.

Mitral valve calcification as an index of left ventricular dysfunction in patients with end-stage renal disease on peritoneal dialysis.

OBJECTIVE: To determine whether mitral valve or anulus calcification (MC) in patients with end-stage renal disease is associated with abnormalities of left ventricular (LV) structure and function, cardiac characteristics of 55 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with (n = 26; age: 59 +/- 10 years) vs without (n = 29; age: 58 +/- 12 years) MC were analyzed using echocardiography and Doppler echocardiography. Sclerosis of the mitral valve anulus was detected in 18 (7 women, 11 men; age: 58 +/- 10 years) patients, sclerosis of mitral valve leaflets in 24 (13 women, 9 men; age: 59 +/- 10 years) patients. Patients with MC had higher systolic arterial blood pressure before initiation of dialysis therapy (191/104 mm Hg vs 173/94 mm Hg; p < 0.05) and higher calcium-phosphorus products (55 +/- 13 vs 42 +/- 16; p < 0.05) during CAPD therapy than those without MC. Neither prevalence nor severity of MC was related to dialysis duration or patient age. Systolic LV function was reduced (ejection fraction: 58 +/- 12 percent vs 65 +/- 13 percent; p < 0.05) and LV end-diastolic diameters were dilated (54 +/- 5 vs 50 +/- 8 mm; p < 0.05) in patients with MC. Left atrial dilatation (73 percent vs 31 percent; p < 0.005) and mitral valve regurgitation (65 percent vs 21 percent; p < 0.001) were more frequent in patients with vs those without MC. Excluding patients with significant mitral regurgitation from pulsed Doppler analysis, diastolic LV function was comparably impaired in patients with vs those without MC (maximal early/atrial filling velocity ratio: 0.77 +/- 0.25 vs 0.75 +/- 0.22; atrial filling fraction: 47 +/- 10 percent vs 48 +/- 11 percent; p = NS). The presented data suggest that MC follows long-standing and severe arterial hypertension before start of dialysis therapy. Therefore, effective blood pressure control in the predialysis period may be a tool to prevent these lesions. MC has clinical significance as a marker of LV dilatation and reduced LV systolic function in patients with chronic CAPD.

[Cardiac characteristics of patients with terminal renal failure after kidney transplantation]. / Kardiale Charakteristika von Patienten mit terminaler Niereninsuffizienz nach Nierentransplantation.

Left ventricular (LV) hypertrophy and dysfunction are risk factors for high mortality from cardiovascular causes in patients with end-stage renal disease. To determine the frequency of these findings after kidney transplantation, 45 patients (11 female, 34 male; age: 47.2 +/- 12 years) after transplantation (57 +/- 37 months) with (n = 21) and without (n = 24) a patent arteriovenous fistula were analyzed with echocardiography. A high prevalence of systolic (> 140 mm Hg: 40%) and diastolic (> 90 mm Hg: 18%) hypertension was observed despite the use of 1.44 +/- 0.9 (range: 0-3) antihypertensive drugs per patient. Most frequent echocardiographic findings were LV hypertrophy (78%; LV mass = 318 +/- 81 g), mostly in the asymmetric septal form (47%; mean ratio septal/posterior wall thicknesses: 1.38 +/- 0.2), and left atrial dilatation (60%; mean diameter: 44 +/- 6 mm). LV dilatation (33%; mean enddiastolic diameter: 53 +/- 5 mm) and systolic dysfunction (20%; mean ejection fraction: 64 +/- 11%) were less common. Individual values of LV mass were directly correlated with systolic blood pressure (p < 0.05). No relation was found between other echocardiographic (LV and left atrial diameters, LV mass, ejection fraction or velocity of circumferential fibre shortening) and clinical (transplantation duration, serum hemoglobin or creatinine, patency of dialysis access, or choice of immunosuppressive therapy) parameters. The presented data suggest that LV hypertrophy is frequent after renal transplantation, and that arterial hypertension is a key factor for the maintenance of LV hypertrophy in these patients, while the patency of the dialysis access, and the durations of transplantation or of preceding dialysis therapy are not relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Course of left ventricular diastolic dysfunction in end-stage renal disease on long-term continuous ambulatory peritoneal dialysis.

To determine factors contributing to abnormal left ventricular (LV) diastolic filling in patients on long-term continuous ambulatory peritoneal dialysis (CAPD), 11 (age: 55 +/- 13 years; CAPD duration: 33 +/- 32 months) out of 42 originally studied CAPD patients were followed over 35 months with echocardiography and pulsed Doppler echocardiography. LV dimensions and systolic function remained normal. Doppler parameters indicated diastolic LV dysfunction in 9/11 patients in the initial study. Despite a significant increase in LV mass (234 +/- 54 vs. 299 +/- 65 g; p < 0.05) and a decrease in LV volume/mass ratios (0.78 +/- 0.18 vs. 0.54 +/- 0.12 ml/g; p < 0.001), no change was observed in any of the diastolic LV filling parameters such as peak early and atrial filling velocities and their ratios, atrial filling fractions and peak filling rate normalized for mitral stroke volume. Individual changes of E/A-max were inversely correlated with systolic blood pressure (p < 0.01), alterations of normalized peak filling rate were inversely correlated with serum creatinine (p < 0.01). No influence on individual changes of LV diastolic filling parameters was observed for LV volume, muscle mass, volume/mass ratios, ejection fractions, patient age, dialysis duration, and hemoglobin concentration. These findings suggest that arterial hypertension and the quality of blood purification play a central role in the development of LV diastolic dysfunction in patients on CAPD, while LV muscle mass and LV volume/mass relations have no relevant influence on changes of LV diastolic function in these patients.

Predictive value of mitral and aortic valve sclerosis for survival in end-stage renal disease on continuous ambulatory peritoneal dialysis.

To determine whether mitral valve or anular sclerosis or calcification (MC) is associated with reduced survival in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD), 53 CAPD patients were followed with echocardiography and Doppler echocardiography over 35 months. Both nonsurvivors and survivors with MC had higher systolic blood pressure before CAPD and calcium-phosphorus products during CAPD treatment than patients without MC (p < 0.05). Serum calcium and phosphorus concentrations, alkaline phosphatase and parathyroid hormone activities were higher in nonsurvivors and survivors with than without MC (p > 0.05). Left ventricular end-diastolic and end-systolic volumes were greater (p < 0.01), ejection fractions were smaller (p < 0.05) in nonsurvivors with than without MC, but not in survivors with versus without MC. Severe MC and grade III mitral valve regurgitation were more frequent in nonsurvivors than in survivors (p < 0.03). No valvular stenoses were found. It is concluded that the development of MC is favored by long-standing predialysis arterial hypertension and by high calcium-phosphorus products during CAPD. Nonsurvivors with MC are characterized by reduced systolic left ventricular function or severe valvular lesions. A close cardionephrologic cooperation is necessary to improve the survival of CAPD patients with these risk factors.

Course of left ventricular hypertrophy and function in end-stage renal disease after renal transplantation.

Cardiovascular complications are frequent and related to left ventricular (LV) hypertrophy and dysfunction in end-stage renal disease. To examine cardiac changes after renal transplantation, 24 hemodialysis patients (18 men and 6 women, age 47 +/- 12 years) were analyzed in a prospective follow-up study with echocardiography immediately before and 41 +/- 30 months after renal transplantation. Mean systolic blood pressure (hemodialysis vs transplantation: 156 +/- 35 vs 144 +/- 15 mm Hg; p = not significant [NS]), as averages of 6 measurements from 2 weeks, remained constant and elevated. The most frequent echocardiographic findings at both assessments were left atrial dilatation (75 vs 79%; p = NS) and LV hypertrophy (71 vs 67%; p = NS). After transplantation, an increase was found in mean left atrial diameter (41 +/- 5 to 44 +/- 5 mm; p < 0.05) and end-diastolic LV diameter (50 +/- 5 to 53 +/- 5 mm; p < 0.05) at constant LV muscle mass (332 +/- 104 vs 329 +/- 94 g; p = NS). LV ejection fraction (58 +/- 10% to 63 +/- 12%; p < 0.02) and stroke volume (98 +/- 26 to 118 +/- 25 ml; p < 0.02) improved. No influence of blood pressure in sporadic morning determinations or of dialysis fistula patency on alterations of LV mass or function was found. Left atrial diameters increased in patients with patent dialysis fistulas (41 +/- 7 to 45 +/- 5 mm; p < 0.05), but not in those with occluded fistulas (41 +/- 7 vs 42 +/- 4 mm; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Diastolic left ventricular function after renal transplantation in patients with normal and hypertrophied myocardium.

While diastolic left ventricular (LV) dysfunction is frequent and associated with cardiovascular complications in end-stage renal disease treated with dialysis, controversial information exists on diastolic LV function after renal transplantation. Therefore, Doppler echocardiographic parameters of LV diastolic filling were analyzed in 17 transplanted patients with normal LV mass (< 150 g/m2; mean: 128 +/- 17 g/m2) and 24 transplanted patients with LV hypertrophy (> 150 g/m2; mean: 197 +/- 36 g/m2) and compared with 28 normal controls without and 11 controls with LV hypertrophy. Mean age (normal vs. increased LV mass: 46 +/- 13 vs. 48 +/- 11 years; p = NS) and transplantation duration (60 +/- 35 vs. 50 +/- 37 months; p = NS) were comparable between renal patients, while systolic blood pressure (136 +/- 12 vs. 149 +/- 14 mmHg; p < 0.02) and serum creatinine (1.55 +/- 0.45 vs. 1.98 +/- 0.76 mg/dl; p < 0.05) were higher in patients with than without LV hypertrophy. In transplanted patients with LV hypertrophy, peak early/atrial filling velocity ratios were decreased (1.17 +/- 0.34 vs. 0.94 +/- 0.34; p < 0.05), mean atrial filling fractions were increased (37 +/- 7% vs. 42 +/- 7%; p < 0.05), and isovolumic relaxation periods were prolonged (86 +/- 23 vs. 106 +/- 26 ms; p < 0.02) compared with transplanted patients with normal LV mass. The frequency of pathologic peak early/atrial filling velocity ratios (12 vs. 42%; p < 0.05), atrial filling fractions (12 vs. 25%; p = NS) and isovolumic relaxation periods (6 vs. 29%; p = NS) was higher in transplanted patients with than without LV hypertrophy. Individual ratios of peak early/atrial filling velocity were inversely correlated with age in transplanted patients with normal LV mass (p < 0.002), and atrial filling fractions were correlated with LV mass index in transplanted patients with LV hypertrophy (p < 0.01). Diastolic LV function was comparable in both groups of transplanted patients with their corresponding non-renal controls. It is concluded that, in transplanted patients, diastolic LV filling is comparable to nonrenal controls; it is age-dependent in patients with normal LV mass and mass-dependent in those with LV hypertrophy.

Progression of valvular sclerosis in end-stage renal disease treated by long-term peritoneal dialysis.

While patients with end-stage renal disease treated by intermittent hemodialysis have frequent and progressive valve disease, nothing is known of the prevalence and course of valvular abnormalities in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Therefore, valves of 24 CAPD patients (ages 55 +/- 11 years; CAPD duration: 29 +/- 28 months) were studied in a prospective echocardiographic and Doppler echocardiographic follow-up analysis over 35 months. Most frequent findings were sclerosis of the aortic annulus (100% at both assessments) and of the anterior mitral valve leaflet (first vs. follow-up assessment: 88 vs. 96%). Sclerosis of the mitral valve annulus (58% vs. 63%), right coronary (54 vs. 63%) and noncoronary (50 vs. 67%) cuspis of the aortic valve and of the posterior mitral valve leaflet (25 vs. 50%) were less frequent but tended to be progressive (p = NS). The moderate form of mitral and aortic valve sclerosis was more frequent than the severe form (p < 0.01 each) at both assessments. Patients with progressive valve disease were older (60 +/- 9 vs. 50 +/- 11 years; p < 0.025) and had a higher frequency angina pectoris than those without a progression (5 vs. 0 patients; p < 0.05). The number of patients with regular sinus rhythm decreased (from 22 to 16; p < 0.03), atrial fibrillation developed in four patients, atrioventricular node rhythm following atrioventricular conduction defect developed in one patient, and atrioventricular conduction defect required implantation of a pacemaker in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Progression of left ventricular hypertrophy in end-stage renal disease treated by continuous ambulatory peritoneal dialysis depends on hypertension and hypercirculation.

To determine whether obvious hemodynamic advantages of continuous ambulatory peritoneal dialysis (CAPD) over intermittent hemodialysis are reflected in superior cardiac structure and function, 16 of 55 analyzed CAPD patients (CAPD duration: 28 months) were followed over 35 months with echocardiography in a prospective analysis: 26 patients had died. LV dimensions (end-diastolic: 52 +/- 7 vs. 51 +/- 8 mm; control vs. follow-up) and systolic function (ejection fraction: 63 +/- 10 vs. 59 +/- 14%) were normal. Major findings were an increase in the amount of initially observed LV hypertrophy (251 +/- 68 vs. 342 +/- 135 g; p less than 0.03) and a decrease in mean LV volume/mass ratios (0.73 +/- 0.17 vs. 0.54 +/- 0.13; p less than 0.001). Excluding patients with dilated cardiomyopathy and valve disease, the amount of progression in LV hypertrophy was related directly to mean arterial pressure and cardiac output (n = 12; p less than 0.02) despite extensive use of antihypertensive medication (1.9 +/- 1.3 vs. 1.5 +/- 1.4 drugs/patient). No correlation was found with diastolic blood pressure, hemoglobin, serum parathyroid hormone, creatinine, urea, age, or CAPD duration. We conclude that LV hypertrophy is frequent in CAPD patients and further increases during long-term CAPD treatment. Factors contributing to the progression of LV hypertrophy are hypertension and hypercirculation.

Cardiovascular factors influencing survival in end-stage renal disease treated by continuous ambulatory peritoneal dialysis.

To determine whether hemodynamic advantages of continuous ambulatory peritoneal dialysis (CAPD) over intermittent hemodialysis are associated with improved survival and identify cardiac risk factors for early death, 55 patients on CAPD (age 58 +/- 11 years; CAPD duration: 29 +/- 25 months) were followed in a noninvasive prospective analysis over 35 months. At follow-up, 25 patients had died; 16 deaths were related to cardiovascular causes. Nonsurvivors were older (62 +/- 8 vs 55 +/- 12 years; p less than 0.015) and had more angina pectoris (40 vs 20%; p less than 0.05) than survivors, but had comparable CAPD duration, arterial blood pressure, hemoglobin, serum creatinine, urea and parathyroid hormone concentrations. On echocardiography, nonsurvivors had a lower mean left ventricular (LV) ejection fraction (59 +/- 15 vs 66 +/- 9%; p less than 0.03), higher LV end-systolic volume indexes (49 +/- 31 vs 36 +/- 13 ml/m2; p less than 0.03) and a shorter mean LV ejection time (371 +/- 41 vs 390 +/- 22 ms; p less than 0.03). LV muscle mass, LV diastolic and left atrial dimensions, stroke volume and cardiac index were comparable. On pulsed Doppler analysis of a subgroup of 48 patients in sinus rhythm and without valve disease, nonsurvivors (n = 23) had more severely decreased ratios of peak early/atrial filling velocities (0.66 +/- 0.18 vs 0.81 +/- 0.24; p less than 0.03) and increased atrial filling fractions (52 +/- 11 vs 46 +/- 9%; p less than 0.03) than survivors. Mean isovolumic relaxation periods were increased in both groups (135 +/- 39 vs 129 +/- 33 ms; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and neurohumoral effects of moxonidine in patients with essential hypertension.

The hemodynamic and neurohumoral effects of a single oral dose (0.4 mg) of the novel centrally acting antihypertensive agent moxonidine were investigated over 4 hours in ten patients with essential hypertension (WHO I-II). Pulmonary pressure indices and cardiac output were determined both at rest and during ergometric exercise by means of Swan-Ganz catheterization. Blood pressure was measured by sphygmomanometry and in the brachial artery. Moxonidine induced a significant fall in blood pressure over the 4-hour observation period from 176/105 mmHg to 158/95 mmHg (p less than 0.01), accompanied by a decrease in systemic vascular resistance from 1695 to 1427 dyn.sec/cm5 (p less than 0.01). Cardiac output remained unchanged, while heart rate increased slightly from 69 to 75 beats/min (p less than 0.01). No significant changes were recorded for either pulmonary artery pressure or pulmonary vascular resistance. Plasma levels of noradrenaline (337 vs. 224 pg/ml) and renin (2.6 vs 2.0 ng/ml/hr) activity fell significantly after moxonidine (p less than 0.05), both at rest and during exercise. Although aldosterone plasma levels fell slightly, level of angiotensin II and ANF remained unchanged. Moxonidine has favorable effects on hemodynamics and the neurohumoral system in patients with essential hypertension and is well tolerated at the dose administered.

Abnormal diastolic left ventricular filling by pulsed Doppler echocardiography in patients on continuous ambulatory peritoneal dialysis.

To determine characteristics of diastolic left ventricular (LV) function in patients on continuous ambulatory peritoneal dialysis (CAPD), two groups of CAPD patients without (n = 23; group 1) vs with (n = 25; group 2) LV hypertrophy (greater than 13 mm) were compared with a group of untreated non-renal hypertensive patients with LV hypertrophy (n = 11; group 3) using Doppler-echocardiography. Age and body surface area were comparable in all three groups, mean CAPD-duration (32 +/- 28 vs 26 +/- 23 months; p = NS) was comparable in renal patients. LV systolic function in echocardiography (LVEF: 62 vs 64 vs 63%) and systolic time intervals were normal and comparable in all three groups. Atrial maximum filling velocities (96 +/- 25 vs 91 +/- 25 vs 67 +/- 8 cm/s) were comparably increased, the ratio of maximal early/atrial filling velocities was comparably decreased (0.73 +/- 0.25 vs 0.77 +/- 0.21 vs 0.99 +/- 0.05) in both groups of renal patients as compared to group 3 (p less than 0.05-0.01). Atrial filling fractions were increased in all three groups, more pronounced in group 1 than in group 3 (50 +/- 11 vs 40 +/- 7%; p less than 0.05). The normal correlation of Doppler parameters with age and with LV radius/thickness ratio was altered in renal patients such that high patient age tended to have an additional negative influence on LV diastolic function of hypertrophied, but not of normal myocardium. Isovolumic relaxation time was prolonged in all three groups (134 +/- 38 vs 131 +/- 34 vs 116 +/- 17 ms; p = NS). We conclude that in patients on CAPD, diastolic LV filling is impaired both in normal and hypertrophied myocardium. High age is a factor that further attributes to diastolic dysfunction of hypertrophied myocardium in CAPD.

Interactions of clonidine and nifedipine in moderately severe hypertensive patients.

In ten patients (age: 47-59 yr) with moderately severe essential hypertension, the humoral and hemodynamic effects of a 4-day therapy with 2 x 75 micrograms clonidine, 2 x 20 mg nifedipine (slow-release), and their combination were investigated and compared with baseline values. The following measurements were observed under clonidine (C), nifedipine (N), and on combination (C/N), respectively: heart rate fell significantly under C from a mean of 79 to 67/min (P less than .05), increased to 73/min after N (P greater than .05) and fell again to 68/min under combination (P less than .05). Systolic blood pressure (Riva-Rocci method) decreased from a mean of 184 to 171 (C), 168 (N) and 161 mm Hg (C/N), respectively (P less than .01). Diastolic blood pressure was also significantly altered (113 vs. 104 (C), 107 (N), and 100 mm Hg (C/N); P less than .05). Stroke volume (ECHO) was not altered significantly (77 vs. 71 (C), 79 (N), and 80 mL (C/N), respectively), whereas cardiac output dropped from 5.9 to 4.9 L/min (C; P less than .05), increased to 5.7 (N; P greater than .05), and dropped again to 5.3 L/min (C/N; P greater than .05). Peripheral vascular resistance increased from a mean of 2091 to 2297 (C), fell to 1933 (N), and increased again to 2138 dyn/sec/cm-5 (C/N). Plasma norepinephrine levels fell from 440 to 281 (C; P less than .01), increased to 391 (N; P greater than .05), and fell again to 404 pg/mL (C/N; P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular muscle mass and diastolic function in patients with essential hypertension under long-term clonidine monotherapy.

To determine whether alterations of left ventricular (LV) structure are associated with improved LV function under chronic clonidine monotherapy (300-450 g/day) of essential hypertension, 11 male patients (age range 47-61 years) were followed for 5.4 +/- 0.9 months using echocardiography and Doppler echocardiography. Blood pressure decreased from a mean of 168/105 to 150/96 mmHg (p less than 0.01), heart rate remained unchanged (73 +/- 10 vs. 71 +/- 10 beats/min). LV muscle mass decreased from 350 +/- 73 to 297 +/- 56 g (p less than 0.02), LV volume/muscle mass ratio increased from 0.58 +/- 0.13 to 0.69 +/- 0.12 ml/g (p less than 0.005). Ejection time increased from 276 +/- 17 to 296 +/- 17 ms (p less than 0.01), whereas no significant change was found for pre-ejection period, ejection fraction, cardiac index and LV dimensions. Doppler analysis revealed improved isovolumic relaxation time (116 +/- 17 vs. 84 +/- 28 ms; p less than 0.05), but no change in isovolumic contraction duration, maximal inflow velocities, time-velocity integrals and their duration, rate of acceleration and deceleration of early and atrial filling, and of their ratios. It is concluded that no reliable improvement in diastolic or systolic LV function is observed in chronic clonidine monotherapy of essential hypertension despite a normalization of blood pressure and a regression of LV hypertrophy.

[Effect of the class IA anti-arrhythmic agents ajmaline on end-systolic pressure-volume relations (conductance technique)]. / Einfluss des Klasse-IA-Antiarrhythmikums Ajmalin auf die endsystolische Druck-Volumen-Beziehung (Conductance-Technik).

To evaluate cardiodepressive risks of antiarrhythmic treatment with ajmaline, we monitored, in addition to conventional hemodynamic parameters, end systolic pressure-volume relations (ESPVR) to assess potential negative inotropic effects. Twelve patients (CAD without ischemia; EF = 60 +/- 3%) underwent hemodynamic analysis with and without the influence of ajmaline (1 mg/kg, i.v.) both 1) at rest (paced heart rate of 90 bpm) and 2) during tachycardia of 160 bpm. As a result, LV-pump function was found to have diminished moderately: EF by 23% vs 10%, respectively; stroke volume by 10% vs 0%; cardiac work by 5% vs 16%, and dP/dtmax by 14% vs 19%. While preload increased under the influence of ajmaline (LVEDP by 17% vs 30%), the LV-volumes increased (EDV by 18% vs 12%; ESV by 58% vs 21%), afterload remained unchanged. Ajmaline caused the loops of the ESPVR to move rightward and the slope k of the ESPVR to decrease, thus indicating loss of inotropy during the influence of the antiarrhythmic agent. Thus, ajmaline showed a tendency to generate cardiodepressive effects in patients with normal LV-function, and to depress contractility in single cases that clinically had no consequences. The conductance technique proved useful and safe in the assessment of inotropic drug effects by analyzing the ESPVR within the catheterization laboratory routine.

Do class 1 antiarrhythmic drugs impair myocardial contractility? The class 1A example of ajmaline (conductance catheter technique).

Antiarrhythmic drug effects may include cardiodepression. This risk is theoretically well recognized but clinically rather poorly defined. To evaluate the risks of ajmaline treatment, we monitored hemodynamic parameters and end-systolic pressure-volume relations (ES-PVR) to evaluate potential negative inotropic effects. Twelve patients (nonischemic CAD) underwent hemodynamic analysis with and without the influence of ajmaline, 1 mg/kg i.v., both (a) at rest (paced constant heart rate of 90 beats/min) and (b) during tachycardia of 160 beats/min. With ajmaline, LV pump function was found to have diminished moderately; ejection fraction by 23 and 10%, stroke volume by 10 and 0%, cardiac work by 5 and 16%, and dP/dtmax by 14 and 19%, respectively. While preload increased under the influence of ajmaline (LVEDP by 17 and 30%, respectively), the LV volumes increased (EDV by 18 and 12%, and ESV by 58 and 21%, respectively), and afterload remained unchanged. Ajmaline caused the loops of the ESPVR to move rightward and the slope k to decrease, thus indicating loss of inotropy under the influence of the antiarrhythmic agent. In essence, ajmaline's negative inotropic components were defined by the conductance technique, but they failed to induce clinically relevant cardiodepression in the above NYHA class II patients. This technique proved to be sensitive, useful, and safe in the assessment of inotropic effects by analyzing the ESPVR within the routine of the catheterization laboratory.

Improved diastolic LV filling after acute application of ajmaline in patients with coronary artery disease and normal systolic LV function.

To determine whether ajmaline (A) can be safely applied in coronary artery disease (CAD), changes of left ventricular (LV) function after acute ajmaline application were analyzed by pulsed Doppler echocardiography in 10 CAD patients. LV pressures in systole and end-diastole and LVEF remained normal and comparable. Doppler normalized peak filling rate (p less than 0.02), peak early/atrial filling velocity (E/A) ratio (p less than 0.01) and E-deceleration (p less than 0.05) increased. The increase in E/A and in E-deceleration relative to base values was directly correlated (p less than 0.001). PEP increased, LVET remained unchanged. LV diastolic filling is improved after acute application of ajmaline in patients with CAD and normal systolic function; its application may be advised not only for therapy of arrhythmia but also to improve left ventricular diastolic mechanics in these patients.