Cardiorenal Syndromes and Their Role in Water and Sodium Homeostasis.

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. Keywords: Cardiorenal syndrome, Renocardiac syndrome, Volume overload, Sodium retention.

A large arteriovenous fistula steals a considerable part of systemic blood flow during veno-arterial extracorporeal circulation support in a porcine model.

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is one of the most frequently used mechanical circulatory support devices. Distribution of extracorporeal membrane oxygenation flow depends (similarly as the cardiac output distribution) on regional vascular resistance. Arteriovenous fistulas (AVFs), used frequently as hemodialysis access, represent a low-resistant circuit which steals part of the systemic perfusion. We tested the hypothesis that the presence of a large Arteriovenous fistulas significantly changes organ perfusion during a partial and a full Veno-arterial extracorporeal membrane oxygenation support. Methods: The protocol was performed on domestic female pigs held under general anesthesia. Cannulas for Veno-arterial extracorporeal membrane oxygenation were inserted into femoral artery and vein. The Arteriovenous fistulas was created using another two high-diameter extracorporeal membrane oxygenation cannulas inserted in the contralateral femoral artery and vein. Catheters, flow probes, flow wires and other sensors were placed for continuous monitoring of haemodynamics and organ perfusion. A stepwise increase in extracorporeal membrane oxygenation flow was considered under beating heart and ventricular fibrillation (VF) with closed and opened Arteriovenous fistulas. Results: Opening of a large Arteriovenous fistulas (blood flow ranging from 1.1 to 2.2 L/min) resulted in decrease of effective systemic blood flow by 17%-30% (p < 0.01 for all steps). This led to a significant decrease of carotid artery flow (ranging from 13% to 25% after Arteriovenous fistulas opening) following VF and under partial extracorporeal membrane oxygenation support. Cerebral tissue oxygenation measured by near infrared spectroscopy also decreased significantly in all steps. These changes occurred even with maintained perfusion pressure. Changes in coronary artery flow were driven by changes in the native cardiac output. Conclusion: A large arteriovenous fistula can completely counteract Veno-arterial extracorporeal membrane oxygenation support unless maximal extracorporeal membrane oxygenation flow is applied. Cerebral blood flow and oxygenation are mainly compromised by the effect of the Arteriovenous fistulas. These effects could influence brain function in patients with Arteriovenous fistulas on Veno-arterial extracorporeal membrane oxygenation.

Comparing the hemodynamic effect of a large arteriovenous fistula during high and low cardiac output states.

Background: A large arteriovenous fistula (AVF) is a low-resistant circuit that affects organ perfusion and systemic hemodynamics even in standard conditions. The extent of its' effect in critical states has not been elucidated yet. We used norepinephrine to create systemic vasoconstriction, dobutamine to create high cardiac output, and rapid right ventricle pacing as a model of acute heart failure in a porcine model of high-flow AVF circulation. Methods: The protocol was performed on nine domestic female pigs under general anesthesia. AVF was created by connecting two high-diameter ECMO cannulas inserted in the femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Three interventions were performed-moderate dose of norepinephrine (0.25 ug/kg/min), moderate dose of dobutamine (10 ug/kg/min) and rapid right ventricle pacing to simulate low cardiac output state with mean arterial pressure under 60 mmHg. Measurements were taken with opened and closed arteriovenous fistula. Results: Continuous infusion of norepinephrine with opened AVF significantly increased mean arterial pressure (+20%) and total cardiac output (CO) (+36%), but vascular resistance remained virtually unchanged. AVF flow (Qa) rise correlated with mean arterial pressure increase (+20%; R = 0.97, p = 0.0001). Effective cardiac output increased, leading to insignificant improvement in organ perfusion. Dobutamine substantially increased cardiac output with insignificant effect on AVF flow and mean arterial pressure. Carotid artery blood flow increased significantly after dobutamine infusion by approximately 30%, coronary flow velocity increased significantly only in closed AVF state. The effective cardiac output using the heart failure model leading to decrease of carotid artery flow and worsening of brain and peripheral tissue oximetry. AVF blood flow also dropped significantly and proportionally to pressure, but Qa/CO ratio did not change. Therefore, the effective cardiac output decreased. Conclusion: In abovementioned extreme hemodynamic conditions the AVF flow was always directly proportional to systemic perfusion pressure. The ratio of shunt flow to cardiac output depended on systemic vascular resistance. These experiments highlight the detrimental role of a large AVF in these critical conditions' models.

Review of the structural and functional brain changes associated with chronic kidney disease.

Chronic kidney disease (CKD) leads to profound metabolic and hemodynamic changes, which damage other organs, such as heart and brain. The brain abnormalities and cognitive deficit progress with the severity of the CKD and are mostly expressed among hemodialysis patients. They have great socio-economic impact. In this review, we present the current knowledge of involved mechanisms.

Factors responsible for cerebral hypoxia in hemodialysis population.

Brain tissue oxygenation (rSO(2)) measured by near-infrared spectroscopy (NIRS) is lower in hemodialysis patients than in the healthy population and is associated with cognitive dysfunction. The involved mechanisms are not known. We conducted this study to identify the factors that influence the rSO2 values in end-stage renal disease (ESRD) patients and to describe rSO2 changes during hemodialysis. We included a cohort of ESRD patients hemodialyzed in our institution. We recorded rSO2 using INVOS 5100C oximetry system (Medtronic, Essex, U.K.) and analyzed changes in basic laboratory values and hemodynamic fluctuations. Baseline rSO2 was lower in patients with heart failure (45.2±8.3 % vs. 54.1±7.8 %, p=0.006) and was significantly linked to higher red cell distribution width (RDW) (r=-0.53, p?0.001) and higher BNP level (r=-0.45, p=0.01). The rSO(2) value decreased in first 15 min of hemodialysis, this decrease correlated with drop in white blood count during the same period (r=0.43, p=0.02 in 10 min, r=0.43, p=0.02 in 20 min). Lower rSO(2) values in patients with heart failure and higher RDW suggest that hemodynamic instability combined with vascular changes probably leads to worse cerebral oxygenation in these patients. Decrease of rSO(2) in 15th minute of hemodialysis accompanied with a significant drop in leukocyte count could be explained by complement activation.

Outcome of resynchronization therapy on superficial and endocardial electrophysiological findings.

Cardiac resynchronization therapy (CRT) has proven efficacious in the treatment of patients with heart failure and dyssynchronous activation. Currently, we select suitable CRT candidates based on the QRS complex duration (QRSd) and morphology with left bundle branch block being the optimal substrate for resynchronization. To improve CRT response rates, recommendations emphasize attention to electrical parameters both before implant and after it. Therefore, we decided to study activation times before and after CRT on the body surface potential maps (BSPM) and to compare thus obtained results with data from electroanatomical mapping using the CARTO system. Total of 21 CRT recipients with symptomatic heart failure (NYHA II-IV), sinus rhythm, and QRSd >/=150 ms and 7 healthy controls were studied. The maximum QRSd and the longest and shortest activation times (ATmax and ATmin) were set in the BSPM maps and their locations on the chest were compared with CARTO derived time interval and site of the latest (LATmax) and earliest (LATmin) ventricular activation. In CRT patients, all these parameters were measured during both spontaneous rhythm and biventricular pacing (BVP) and compared with the findings during the spontaneous sinus rhythm in the healthy controls. QRSd was 169.7+/-12.1 ms during spontaneous rhythm in the CRT group and 104.3+/-10.2 ms after CRT (p<0.01). In the control group the QRSd was significantly shorter: 95.1+/-5.6 ms (p<0.01). There was a good correlation between LATmin(CARTO) and ATmin(BSPM). Both LATmin and ATmin were shorter in the control group (LATmin(CARTO) 24.8+/-7.1 ms and ATmin(BSPM) 29.6+/-11.3 ms, NS) than in CRT group (LATmin(CARTO) was 48.1+/-6.8 ms and ATmin(BSPM) 51.6+/-10.1 ms, NS). BVP produced shortening compared to the spontaneous rhythm of CRT recipients (LATmin(CARTO) 31.6+/-5.3 ms and ATmin(BSPM) 35.2+/-12.6 ms; p<0.01 spontaneous rhythm versus BVP). ATmax exhibited greater differences between both methods with higher values in BSPM: in the control group LATmax(CARTO) was 72.0+/-4.1 ms and ATmax (BSPM) 92.5+/-9.4 ms (p<0.01), in the CRT candidates LATmax(CARTO) reached only 106.1+/-6.8 ms whereas ATmax(BSPM) 146.0+/-12.1 ms (p<0.05), and BVP paced rhythm in CRT group produced improvement with LATmax(CARTO) 92.2+/-7.1 ms and ATmax(BSPM) 130.9+/-11.0 ms (p<0.01 before and during BVP). With regard to the propagation of ATmin and ATmax on the body surface, earliest activation projected most often frontally in all 3 groups, whereas projection of ATmax on the body surface was more variable. Our results suggest that compared to invasive electroanatomical mapping BSPM reflects well time of the earliest activation, however provides longer time-intervals for sites of late activation. Projection of both early and late activated regions of the heart on the body surface is more variable than expected, very likely due to changed LV geometry and interposed tissues between the heart and superficial ECG electrode.

Electrocardiographic outcome of resynchronization therapy.

Cardiac resynchronization therapy (CRT) has proven efficacious in reducing or even eliminating cardiac dyssynchrony and thus improving heart failure symptoms. However, quantification of mechanical dyssynchrony is still difficult and identification of CRT candidates is currently based just on the morphology and width of the QRS complex. As standard 12-lead ECG brings only limited information about the pattern of ventricular activation, we aimed to study changes produced by different pacing modes on the body surface potential maps (BSPM). Total of 12 CRT recipients with symptomatic heart failure (NYHA II-IV), sinus rhythm and QRS width >/=120 ms and 12 healthy controls were studied. Mapping system Biosemi (123 unipolar electrodes) was used for BSPM acquisition. Maximum QRS duration, longest and shortest activation times (ATmax and ATmin) and dispersion of QT interval (QTd) were measured and/or calculated during spontaneous rhythm, single-site right- and left-ventricular pacing and biventricular pacing with ECHO-optimized AV delay. Moreover we studied the impact of CRT on the locations of the early and late activated regions of the heart. The average values during the spontaneous rhythm in the group of patients with dyssynchrony (QRS 140.5+/-10.6 ms, ATmax 128.1+/-10.1 ms, ATmin 31.8+/-6.7 ms and QTd 104.3+/-24.7 ms) significantly differed from those measured in the control group (QRS 93.0+/-10.0 ms, ATmax 79.1+/-3.2 ms, ATmin 24.4+/-1.6 ms and QTd 43.6+/-10.7 ms). Right ventricular pacing (RVP) improved significantly only ATmax [111.2+/-10.6 ms (p<0.05)] but no other measured parameters. Left ventricular pacing (LVP) succeeded in improvement of all parameters [QRS 105.1+/-8.0 ms (p<0.01), ATmax 103.7+/-7.1 ms (p<0.01), ATmin 20.2+/-3.7 ms (p<0.01) and QTd 52.0+/-9.4 ms (p<0.01)]. Biventricular pacing (BVP) showed also a beneficial effect in all parameters [QRS 121.3+/-8.9 ms (p<0.05), ATmax 114.3+/-8.2 ms (p<0.05), ATmin 22.0+/-4.1 ms (p<0.01) and QTd 49.8+/-10.0 ms (p<0.01)]. Our results proved beneficial outcome of LVP and BVP in evaluated parameters (what seems to be important particularly in the case of activation times) and revealed a complete return of activation times to normal distribution when using these CRT modalities.