Effect of monoclonal anti-ANP antibodies on the acute functional adaptation to unilateral nephrectomy

Effect of monoclonal anti-ANP antibodies on the acute functional adaptation to unilateral nephrectomy. The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administration of monoclonal anti-ANP antibodies. The circulating ANP levels almost tripled (from 23 ± 4 to 66 ± 13 fmol/ml, P < 0.01) within two minutes after UNX, whereas no change resulted from sham intervention. In the control group receiving vehicle injection, UNX resulted in a twofold increase in urinary sodium excretion (from 1.39 ± 0.25 to 2.88 ± 0.28 µmol/min, P < 0.01) related to a decrease in the fractional reabsorption of sodium at both proximal and distal sites (estimated from fractional excretion of lithium). Urinary excretion of cyclic guanosine 3′-5′-monophosphate (cGMP) increased as well, but glomerular filtration rate did not change. In addition, UNX was associated with a short-lived (<20 min) rise in systemic arterial pressure and a transient fall in right atrial pressure. Administration of monoclonal anti-ANP antibodies totally prevented the UNX-associated natriuresis by blunting both proximal and distal tubular reabsorption of sodium, and suppressed the rise in urinary cGMP excretion following UNX. The duration of the post-UNX increase in arterial pressure was longer when compared to values observed in controls. These observations indicate that ANP release is stimulated after uninephrectomy. UNX-induced changes in arterial pressure and electrolyte excretion are altered by administration of anti-ANP antibodies, thus suggesting that ANP may be an important mediator of the acute adaptation to unilateral renal ablation

Acute echocardiographic and electrocardiographic effects of triggered left ventricular pacing

Cardiac resynchronization therapy (CRT) is an essential pillar in the therapy of heart failure patients with reduced ejection fraction (HFrEF) presenting with broad left bundle branch block (LBBB) or pacemaker dependency. To achieve beneficial effects, CRT requires high bi-ventricular (BiV) pacing rates. Therefore, device-manufacturers designed pacing algorithms which maintain high BiV pacing rates by a left ventricular (LV) pacing stimulus immediately following a right ventricular sensed beat. However, data on clinical impact of these algorithms are sparse. We studied 17 patients implanted with a CRT device providing triggered left ventricular pacing (tLVp) in case of atrioventricular nodal conduction. Assessment of LV dyssynchrony was performed using echocardiographic and electrocardiographic examination while CRT-devices were set to three different settings: 1. Optimized bi-ventricular-stimulation (BiV); 2. Physiological AV nodal conduction (tLVp-off); 3. Physiological AV nodal conduction and tLVp-algorithm turned on (tLVp-on). QRS duration increased when the CRT-device was set to tLVp-off compared to BiV-Stim, while QRS duration was comparable to BiV-Stim with the tLVp-on setting. Echocardiographic analysis revealed higher dyssynchrony during tLVp-off compared to BiV-Stim. TLVp-on did not improve LV dyssynchrony compared to tLVp-off. QRS duration significantly decreased using tLVp-algorithms compared to physiological AV nodal conduction. However, echocardiographic examination could not show functional benefit from tLVp-algorithms, suggesting that these algorithms are inferior to regular biventricular pacing regarding cardiac resynchronization. Therefore, medical treatment and ablation procedures should be preferred, when biventricular pacing rates have to be increased. TLVp-algorithms can be used in addition to these treatment options

Fig 5 -

(A) QRS width; (B) Max. LV delay depending on the amount of QRS shortening by tLVp with regard to intrinsic QRS complex (BiV–biventricular pacing, LV—left ventricle, tLVp—triggered left ventricular pacing); n = 9 for ≤20ms, n = 8 for >20ms.</p

Fig 1 -

Electrogram (EGM) and electrocardiogram (ECG) of the three different settings: 1. optimized bi-ventricular-stimulation (BiV); 2. Physiological AV nodal conduction without triggered left ventricular pacing (tLVp-off); 3. TLVp algorithm turned on (tLVp-on) with physiological AV nodal conduction (a), and after premature ventricular contraction (PVC; b). (ECG–electrocardiogram, IEGM–internal electrogram, PVC—premature ventricular contraction, tLVp—triggered left ventricular pacing).</p

Echocardiographic (echo) markers in the different CRT modes.

(A) 3D LVEF (echo); (B) Systolic dyssynchrony index (SDI; echo). (3D - 3-dimensional, BiV–biventricular pacing, LV—left ventricle, LVEF–left ventricular ejection fraction, tLVp—triggered left ventricular pacing).</p

Patient characteristics (n = 17).

Patient characteristics (n = 17).</p

LV delay, measured by 2D strain (echo) in the different CRT modes.

Max. (BiV–biventricular pacing, LV—left ventricle, LVEF–left ventricular ejection fraction, tLVp—triggered left ventricular pacing).</p

QRS width (ecg) in the different CRT modes.

(BiV–biventricular pacing, LV—left ventricle, tLVp—triggered left ventricular pacing).</p

Electrocardiographic and echocardiographic markers depending on the amount of QRS shortening by tLVp with regard to intrinsic QRS complex.

Electrocardiographic and echocardiographic markers depending on the amount of QRS shortening by tLVp with regard to intrinsic QRS complex.</p

Correlations of intermediate monocytes with cortisol, aldosterone and noradrenaline.

<p>Correlations (Spearman) between intermediate monocyte measured by flow cytometry and cortisol (cor), aldosterone (aldo) as well as noradrenaline (nor). (a) Intermediate monocyte pre TAVR vs. cor, aldo, nor pre TAVR. (b) Intermediate monocyte post TAVR vs. cor, aldo, nor post TAVR. Correlations among cor, aldo and nor are also shown. On the top of each graph: pairwise correlation value and relative significance (negative value indicates inverse correlation); on bottom: bivariate scatterplot. ** p<0.01.</p