Hemodynamic Response to Exercise for Prediction of Development of Kidney Failure: Revealing a Cardiorenal Secret Cross Talk.

INTRODUCTION: Kidney disease increases the risk of cardiovascular disease. The corollary of that observation should be that cardiovascular disease would not only increase the risk of kidney dysfunction, but also cause kidney damage, a concept not previously proposed. MATERIALS AND METHODS: Hemodynamic response to a graded exercise stress test was measured in 70 candidates to evaluate the association of heart rate and blood pressure change, heart rate reserve, chronotropic incompetence (percentage of achievement of maximal predicted heart rate), and circulatory power with development of kidney failure (glomerular filtration rate < 30 mL/min/1.73 m2) during 123 months of follow-up period. RESULTS: Kidney failure was more likely to develop in patients with lower heart rate change, heart rate reserve, percentage of achievement of maximal predicted heart rate, and circulatory power (P = .002, P = .01, P = .02, and P = .008, respectively), even after adjustment for age, resting pulse pressure, hypertension, diabetes mellitus, and exercise test result (hazard ratios, 5.9, 2.9, 3.3, and 2.9, respectively). A resting pulse pressure of 60 mm Hg and higher was accompanied by 7.4 times (95% confidence interval, 1.8 to 30.9) greater risk of developing kidney failure, independent of age and resting systolic blood pressure (P = .006). CONCLUSIONS: Hemodynamic responses to a standard graded exercise stress test independently predicted the development of kidney failure. Also, arterial stiffness (represented by resting pulse pressure) could be a factor linking ventricular and kidney function. Early diagnosis of kidney disease should include a cardiovascular assessment and vice versa.

Differential effects of inhaled methacholine on circumferential wall and vascular smooth muscle of third-generation airways in awake sheep.

Evolution and natural selection ensure that specific mechanisms exist for selective airway absorption of inhaled atmospheric molecules. Indeed, nebulized cholinoceptor agonists used in asthma-challenge tests may or may not enter the systemic circulation. We examined the hypothesis that inhaled cholinoceptor agonists have selective access. Six sheep were instrumented under general anesthesia (propofol 5 mg/kg iv, 2-3% isoflurane-oxygen), each with pulsed-Doppler blood flow transducers mounted on the single bronchial artery and sonomicrometer probes mounted on the intrapulmonary third-generation lingula lobe bronchus. Continuous measurements were made of bronchial blood flow (Q(br)), Q(br) conductance (C(br)), bronchial hemicircumference (CIRC(br)), and bronchial wall thickness (WALL TH(br)) in recovered, standing, awake sheep. Methacholine (MCh; 0.125-2.0 µg/kg iv), at the highest dose, caused a 233% rise in Q(br) (P < 0.05) and a 286% rise in C(br) (P < 0.05). CIRC(br) fell to 90% (P < 0.05); WALL TH(br) did not change. In contrast, nebulized MCh (1-32 mg/ml), inhaled through a mask at the highest dose, caused a rise in ventilation and a rise in Q(br) proportional to aortic pressure without change in C(br). CIRC(br) fell to 91% (P < 0.01), and WALL TH(br) did not change. Thus inhaled MCh has access to cholinoceptors of bronchial circumferential smooth muscle to cause airway lumen narrowing but effectively not to those of the systemic bronchovascular circulation. It is speculated that the mechanism is selective neuroparacrine inhibition of muscarinic acetylcholine receptors (M3 bronchovascular cholinoceptors) by prostanoids released by intense MCh activation of epithelial and mucosal cells lining the airway.

Disturbed hemodynamic cardiac exercise stress test response in non-smoking, normolipidemic, normotensive, diabetic subjects.

OBJECTIVE: The hemodynamic response to exercise is affected by diverse factors such as age, gender and exercise load as well as concomitant pathogenic conditions including smoking, hyperlipidemia, hypertension and possibly diabetes. In this study the hemodynamic response to a graded exercise has been evaluated in diabetic and non-diabetic individuals. DESIGN AND METHOD: In 3170 consecutive non-smoker normolipidemic normotensive patients, referred for the treadmill exercise test (age 25-70 years), the exercise-induced change in heart rate (DeltaHR) and blood pressure (DeltaSBP and DeltaDBP) was evaluated in 176 diabetics (DM) compared to non-diabetics (NDM). RESULTS: The results demonstrated that while resting HR and SBP were higher in DM, they had an impaired DeltaHR (62.1+/-20.5 versus 76.4+/-24.2; P<0.0001), DeltaSBP (35.5+/-29.3 versus 42.2+/-24.5; P<0.01) and DeltaDBP (-0.4+/-9.8 versus 2.1+/-15.9; P<0.05) in response to exercise compared to NDM, even among individuals with negative results for exercise test. DM had also lower heart rate reserve, circulatory power and rate-pressure product than NDM (all P<0.0001). While DM were slightly older (57 versus 54.5) and had lower exercise capacity (7.1 versus 8.6 MET) than NDM (both P<0.01), the impact of DM on the hemodynamic changes remained independent and significant after multivariate adjustment for age, exercise load and gender for DeltaHR and DeltaSBP (P<0.01). Exercise-induced DeltaSBP was directly correlated with exercise load and inversely associated with resting pulse pressure (rPP) (P<0.0001). Furthermore, rPP was the second strongest independent predictor for DeltaSBP (beta=-0.22, p<0.0001). CONCLUSION: The impaired hemodynamic response of DM to exercise and its inverse association with rPP supports the early development of arterial and ventricular stiffness in DM, unrelated to other likely risk factors such as hypertension and hyperlipidemia.