The effects of extracellular volume and intradialytic peripheral resistance changes on ambulatory blood pressure in hemodialysis patients with and without recurrent intradialytic hypertension

Background Hypertension and extracellular volume (ECV) overload are interrelated mortality risk factors in hemodialysis (HD) patients, but confounding related to changes in ECV and vasoconstriction during and between treatments obfuscate their relationship. We sought to clarify independent contributions of post-HD ECV and intradialytic changes in vasoconstriction on ambulatory blood pressure (BP) in patients with and without recurrent intradialytic hypertension (IH). Methods In this prospective observational study, we obtained measurements of pre- and post-HD ECV with bioimpedance spectroscopy (BIS), pre- and post-HD total peripheral resistance index and 44-h ambulatory BP. Linear regression determined associations between post-HD ECV/weight and intradialytic change in total peripheral resistance index (TPRI) with interdialytic BP and slope. Results In fully-adjusted models for participants with complete data, post-HD ECV/weight associated with mean ambulatory BP (β = 133, P = 0.01; n = 52) and ambulatory BP slope (β = −4.28, P = 0.03; n = 42). ECV/weight was associated with mean ambulatory BP in those with recurrent IH (β = 314, P = 0.0005; n = 16) and with ambulatory BP slope in those without recurrent IH (β = −4.56, P = 0.04; n = 28). Interdialytic weight gain percentage and intradialytic TPRI change were not associated with ambulatory BP or slope in any analyses. Conclusion Ambulatory BP in HD patients is more strongly associated with post-HD ECV assessed with BIS than with intradialytic TPRI changes or interdialytic ECV increases. These findings highlight the essential role of recognizing and managing chronic ECV overload to improve ambulatory BP in HD patients, particularly so for those with IH.

Cardiovascular Effects of Stress During Acutely Increased Free Fatty Acids in a Randomized, Double-Blind, Cross-Over Study in Humans

Increased free fatty acids stimulate sympathetic nervous system activity, impair endothelium-dependent vasodilation, and increase regional blood flow. The aim of this study was to assess if fatty acids acutely elevated by infusion of intralipid/heparin affect cardiovascular reactivity employing two stressors eliciting either a cardiac (Stroop test) or vascular (Cold Face test) dominated pressor response. Two stress tasks were performed in 20 healthy subjects (10 women, 10 men) before and during a 180-min intralipid/heparin or saline infusion as placebo on alternate trial days in a randomized crossover study design. Blood pressure, heart rate, cardiac index, and total peripheral resistance index were measured. At baseline, the Stroop test did not affect hemodynamic parameters, and the Cold Face test had an impact on hemodynamic parameters except for heart rate. Plasma fatty acids concentrations increased to 810% (t=11.0, p<0.001) of baseline and C-peptide increased by 17% (t=4.66, p<0.001) during intralipid/heparin infusion. This was paralleled by increased cardiac index (F=9.98; p<0.005 vs. saline) and reduced total peripheral resistance index (F=4.46; p<0.05 vs saline). There was no effect of intralipid/heparin or saline infusion on Stroop test or Cold Face test reactivity of hemodynamic parameters. An acute increase in free fatty acids does not affect the magnitude or pattern of stress response in healthy volunteers, but primarily alter the underlying cardiovascular tone by decreasing total peripheral resistance index and increasing cardiac index to maintain a constant blood pressure.

Peripheral chemoreceptor control of cardiovascular function at rest and during exercise in heart failure patients

Peripheral chemoreceptor activity/sensitivity is enhanced in chronic heart failure (HF), and sensitivity is linked to greater mortality. This study aimed to determine the role of the peripheral chemoreceptor in cardiovascular control at rest and during exercise in HF patients and controls. Clinically stable HF patients ( n = 11; ejection fraction: 39 ± 5%) and risk-matched controls ( n = 10; ejection fraction: 65 ± 2%) performed randomized trials with or without dopamine infusion (2 μg·min−1·kg−1) at rest and during 40% maximal voluntary contraction handgrip (HG) exercise, and a resting trial of 2 min of inspired 100% oxygen. Both dopamine and hyperoxia were used to inhibit the peripheral chemoreceptor. At rest in HF patients, dopamine decreased ventilation ( P = 0.02), decreased total peripheral resistance index ( P = 0.003), and increased cardiac and stroke indexes ( P ≤ 0.01), yet there was no effect of dopamine on these variables in controls ( P ≥ 0.7). Hyperoxia lowered ventilation in HF ( P = 0.01), but not in controls ( P = 0.9), indicating suppression of the peripheral chemoreceptors in HF. However, no decrease of total peripheral resistance index was observed in HF. As expected, HG increased heart rate, ventilation, and brachial conductance of the nonexercising arm in controls and HF patients. During dopamine infusion, there were no changes in mean arterial pressure, heart rate, or ventilation responses to HG in either group ( P ≥ 0.26); however, brachial conductance increased with dopamine in the control group ( P = 0.004), but decreased in HF ( P = 0.02). Our findings indicate that the peripheral chemoreceptor contributes to cardiovascular control at rest in HF patients and during exercise in risk-matched controls.

Enhanced vascular effects of the Ca2+ channel agonist Bay K 8644 in pregnant rabbits

Hemodynamic studies were performed to determine if blunting of vascular pressor responsiveness to vasoconstrictors during pregnancy may be due to impaired L-type voltage-dependent calcium channels (L-VDCC). Bay K 8644 (BAY), an L-VDCC agonist, was infused in pregnant and nonpregnant anesthetized rabbits (10, 20, 40, and 60 μg/kg) and pregnant and nonpregnant conscious, chronically instrumented (conscious) rabbits (10, 25, and 50 μg/kg). BAY infusions resulted in greater elevation of mean arterial pressure in both anesthetized pregnant ( n = 6) vs. nonpregnant ( n = 6) ( P < 0.05) and conscious pregnant ( n = 10) vs. nonpregnant ( n = 10) rabbits ( P < 0.05). Fractional increase over baseline of total peripheral resistance index was greater in pregnant (36 ± 5 to 78 ± 14%) vs. nonpregnant rabbits (14 ± 4 to 52 ± 6%) ( P< 0.02). Cardiac output index did not differ. There was a single high-affinity L-VDCC antagonist aortic binding site with similar number and affinity in pregnant ( n = 7) and nonpregnant ( n = 7) rabbits. In conclusion, stimulation of L-VDCC induces greater pressor responses in pregnant rabbits with heightened peripheral vasoconstriction. This does not appear to be due to a change in L-VDCC receptor parameters.

Hemodynamic responses to paraventricular nucleus disinhibition with bicuculline in conscious rats

The present study was undertaken to determine the hemodynamic responses associated with stimulation of the hypothalamic paraventricular nucleus (PVN). Male Sprague-Dawley rats (n = 21) were instrumented with guide cannulas directed bilaterally at the PVN, with an electromagnetic flow probe placed on the ascending aorta and with femoral venous and arterial catheters. Bicuculline methiodide (BMI, 2 mM) was infused bilaterally (100 nl/20 min) into the PVN region before and after treatment with the beta 1-adrenergic antagonist, metoprolol bitartrate (2 mg/kg iv) or the alpha 1-adrenergic receptor antagonist, prazosin hydrochloride (2 mg/kg iv). Infusion of BMI into the PVN increased mean arterial pressure by 17 +/- 2 mmHg, and heart rate rose by 91 +/- 8 beats/min. Cardiac index increased 17 +/- 3%, whereas total peripheral resistance index was not altered significantly. After metoprolol treatment, the mean arterial pressure response to BMI was similar to control (16 +/- 2 mmHg), but the tachycardia was reduced significantly (10 +/- 4 beats/min). In addition, the blood flow response was changed qualitatively. Total peripheral resistance increased 13 +/- 3%, whereas the cardiac index response was abolished (1 +/- 2%). After prazosin treatment, BMI administration into the PVN failed to increase arterial pressure (-1 +/- 4 mmHg). Nevertheless, the BMI infusion was associated with significant hemodynamic effects. Total peripheral resistance index decreased (-24 +/- 6%), whereas cardiac index and stroke volume index increased 34 +/- 8 and 17 +/- 5%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic monitoring for 24 h in unanesthetized rats

A new technique is described that allows minute-to-minute recordings of cardiac output and arterial pressure in unanesthetized rats for periods of 24 h and longer. Rats were instrumented with electromagnetic flow probes and arterial catheters. An electrical and hydraulic swivel was interposed between the rat and recording apparatus to allow free range of movement. Data were collected and analyzed once each minute by computer. Average 24-h values (mean +/- SD) for the following hemodynamic variables were determined in eight rats [expressed where appropriate as a function of body weight (BW)]: cardiac output (98.1 +/- 14.7 ml/min), cardiac index (29.2 +/- 4.4 ml.min-1.100 g BW-1), mean arterial pressure (92.5 +/- 7.8 mmHg), heart rate (347 +/- 45 beats/min), peak aortic flow (403 +/- 32 ml/min), stroke volume (282 +/- 26 microliters), stroke volume index (84.4 +/- 8.1 microliters/100 g BW), and total peripheral resistance index (3.26 +/- 0.46 mmHg.ml-1.min.100 g BW). These results provide a data base of hemodynamic values for unanesthetized adult, Sprague-Dawley male rats, which has not been previously available. In addition, cardiac index, mean arterial pressure, and total peripheral resistance index demonstrated diurnal variation. Diurnal variation contributed substantially to the overall variance observed within these variables. Hourly variance was also substantial and indicates the use of continuous recordings for short-term experiments.

Thyrotropin releasing hormone in hypovolemia: a hemodynamic evaluation in the rat

In the present study the effects of thyrotropin releasing hormone (TRH) and its stable analogue, CG3703, on cardiac output (thermodilution, Cardiomax) and regional blood flow (BF; directional pulsed Doppler technique) were investigated in hypovolemic hypotension in the rat. In urethan-anesthetized rats TRH (0.5 or 2 mg/kg ia) or CG3703 (0.05 or 0.5 mg/kg ia) reversed the bleeding (27% of the blood volume)-induced decreases in mean arterial pressure (MAP) and cardiac index (CI) and increased the heart rate (HR) and total peripheral resistance index (TPRI) in a dose-related manner. In the conscious rat exposed to a 45% hemorrhage, CG3703 (0.5 mg/kg ia) significantly raised MAP, HR, and TPRI with maximum changes of +67 +/- 6 (SE) mmHg, +123 +/- 30 beats/min, and +101 +/- 2%, respectively, CG3703 (0.5 mg/kg ia) also further enhanced the hemorrhage-induced reduction of hindquarter, mesenteric, and renal BF. The changes in BF in saline-treated vs. CG3703-treated rats 2 h after the bleeding were -32 +/- 6 vs. -55 +/- 6% (P less than 0.001) in hindquarter, -9 +/- 8 vs. -61 +/- 11% (P less than 0.001) in mesenteric, and -2 +/- 9 vs. -33 +/- 9% (P less than 0.01) in the renal artery; the changes in vascular resistance +30 +/- 7 vs. +309 +/- 167% (P less than 0.001) in hindquarter, -4 +/- 8 vs. +349 +/- 244% in the mesenteric, and -10 +/- 9 vs. +80 +/- 10% (P less than 0.01) in the renal artery. The survival rate after the 45% hemorrhage was significantly reduced by both TRH and CG3703.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of 1 Year's Therapy in Essential Hypertension on Systemic Haemodynamics Studied before and after ‘Total’ Autonomic Blockade

1. The haemodynamics of ten patients with essential hypertension were studied before treatment (study 1) and again 1 week after cessation of 1 year's antihypertensive drug therapy (study 2). On each occasion measurements of mean arterial pressure (MAP), cardiac index (CI) and total peripheral resistance index (TPRI) were made before and after ‘total’ pharmacological autonomic blockade (with intravenous propranolol, atropine, phentolamine and clonidine); measurements after ‘total’ autonomic blockade were used to assess the magnitude of the ‘non-autonomic’ component of TPRI, which reflects humoral or structural alterations in the vasculature. 2. The findings before ‘total’ autonomic blockade during study 2 showed that MAP was 18 ± 8 mmHg below the value (135 mmHg) observed during study 1 before treatment, and TPRI had fallen by 33% (P &lt; 0·05) and CI had increased by 23% (P &lt; 0·05). 3. After ‘total’ autonomic blockade the differences in the ‘non-autonomic’ components of the different variables were similar, with ‘non-autonomic’ MAP 14 ± 4 mmHg lower in study 2, TPRI 42% lower (P &lt; 0·005) and CI 28% higher. The value in ‘non-autonomic’ TPRI was now the same as values previously observed in normotensive subjects. 4. We conclude that after 1 year's successful treatment there is complete restoration of ‘non-autonomic’ TPRI as a secondary consequence of the blood pressure reduction.