Introduction: Reperfusion is required to salvage ischaemic tissue, but also causes further damage (i.e., ischaemia/reperfusion-injury). Heart failure patients reveal exaggerated ischaemia/reperfusion-injury, whilst traditional ischaemic preconditioning cannot prevent ischaemia/reperfusion-injury. Exercise training may be a more powerful preconditioning stimulus, especially high-intensity interval training given the similarities with ischaemic preconditioning. Therefore, we examined the impact of 12-week continuous training vs. high-intensity interval training on brachial artery endothelial ischaemia/reperfusion-injury in heart failure patients New York Heart Association-class II-III.Methods: Twenty heart failure patients (male:female 19:1, 64 ± 8 years, ejection fraction 38 ± 6%) were allocated to 12-weeks of high-intensity interval training (10∗1-min 90% maximal workload – 2.5-min 30% maximal workload) or continuous training (30-min 60–75% maximal workload). Before and after the intervention, we measured brachial artery endothelial function with flow-mediated dilation (FMD) before and after ischaemia/reperfusion (5-min ischemic exercise, 15-min reperfusion).Results: Ischaemia/reperfusion caused a significant decline in FMD (continuous training (n = 10): 5.2 ± 2.5 to 3.4 ± 1.6%, high-intensity interval training (n = 10): 5.3 ± 2.6 to 3.5 ± 1.6%, P = 0.01), which was not different between groups (P > 0.05). Training improved maximal workload and fitness (P < 0.05), with no differences between groups (P > 0.05). Exercise training did not alter FMD (P > 0.05), whilst ischaemia/reperfusion did not impair FMD after exercise training (continuous training: 4.8 ± 3.0 to 4.2 ± 2.3%, high-intensity interval training: 4.7 ± 2.5 to 3.8 ± 2.3%, P > 0.05). No changes were found in FMD before or after ischaemia/reperfusion after 12-weeks in controls (n = 9).Conclusion: We found that 12-week exercise training in heart failure patients mitigated endothelial ischaemia-reperfusion injury, an effect independent of the type of exercise. These changes may contribute to the cardioprotective effects of exercise training, whilst our findings highlight the potency of exercise as a preconditioning stimulus.

What is the central question of this study? What is the role of carbon dioxide in the cerebral blood flow (CBF) response to the cold pressor test (CPT)? What is the main finding and its importance? The CBF response was elevated during the isocapnic (controlled CO ) CPT in the middle cerebral artery and the internal carotid artery compared with the poikilocapnic (uncontrolled CO ) CPT, owing to ventilation-associated reductions in end-tidal CO . Furthermore, the common carotid artery vasodilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, whereas the internal carotid artery vasoconstricted during both CPTs. Our data highlight the importance of CO control when investigating the CBF response to the CPT. In addition to increasing sympathetic nervous activity, blood pressure and cerebral blood flow (CBF), the cold pressor test (CPT) stimulates pain receptors, which may increase ventilation above metabolic demand; this response is likely to reduce the partial pressure of end-tidal carbon dioxide (P ET ,CO2) and will attenuate elevations in CBF. Our hypotheses were as follows: (i) the CPT will elicit hyperventilation, effectively lowering P ET ,CO2; (ii) the CBF response will be elevated during an isocapnic (controlled P ET ,CO2) compared with a poikilocapnic CPT (uncontrolled P ET ,CO2); and (iii) in response to the CPT, the common carotid artery (CCA) will vasodilate, while the internal carotid artery (ICA) will remain unchanged to help regulate CBF. Using a new, randomized experimental design, we measured the cerebrovascular response in the middle cerebral artery (MCA), CCA and internal carotid artery (ICA), during an isocapnic and poikilocapnic CPT in 15 participants. Blood pressure and cardiac output (finger photoplethysmography), heart rate (ECG), MCA mean velocity (transcranial Doppler ultrasound) and CCA and ICA CBF (Duplex ultrasound) were recorded during both CPT trials. Our findings were as follows: (i) ventilation increased, which reduced P ET ,CO2 (-5.3 ± 6.4 mmHg) during the poikilocapnic compared with the isocapnic CPT; (ii) the CBF response was elevated during the isocapnic compared with the poikilocapnic CPT in the MCA and ICA, but not in the CCA; and (iii) the CCA dilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, and the ICA vasoconstricted during both trials. Our data emphasize the importance of P ET ,CO2 control in the CBF response to the CPT and in the differential vasomotor regulation between the CCA and ICA.

Carotid artery (CCA) dilation occurs in healthy subjects during cold pressor test (CPT), while the magnitude of dilation relates to cardiovascular risk. To further explore this phenomenon and mechanism, we examined carotid artery responses to different sympathetic tests, with and without α-receptor blockade and assessed similarity to these responses between carotid and coronary arteries. In randomized order, 10 healthy participants (25 ± 3 yr) underwent sympathetic stimulation using the CPT (3-min left-hand immersion in ice-slush) and lower-body negative pressure (LBNP). Before and during sympathetic tests, CCA diameter and velocity (Doppler ultrasound) and left anterior descending (LAD) coronary artery velocity (echocardiography) were recorded across 3 min. Measures were repeated 90 min following selective α-receptor blockade via oral prazosin (0.05 mg/kg body wt). CPT significantly increased CCA diameter, LAD maximal velocity, and velocity-time integral area-under-the-curve (all P < 0.05). In contrast, LBNP resulted in a decrease in CCA diameter, LAD maximal velocity, and velocity time integral (VTI; all P < 0.05). Following α-receptor blockade, CCA and LAD velocity responses to CPT were diminished. In contrast, during LBNP (-30 mmHg), α-receptor blockade did not alter CCA or LAD responses. Finally, changes in CCA diameter and LAD VTI responses to sympathetic stimulation were positively correlated ( r = 0.66, P < 0.01). We found distinct carotid artery responses to different tests of sympathetic stimulation, where α receptors partly contribute to CPT-induced responses. Finally, we found agreement between carotid and coronary artery responses. These data indicate similarity between carotid and coronary responses to sympathetic tests and the role of α receptors that is dependent on the nature of the sympathetic challenge. NEW & NOTEWORTHY We showed distinct carotid artery responses to cold pressor test (CPT; i.e., dilation) and lower-body negative pressure (LBNP; i.e., constriction). Blockade of α-receptors significantly attenuated dilator responses in carotid and coronary arteries during CPT, while no changes were found during LBNP. Our findings indicate strong similarity between carotid and coronary artery responses to distinct sympathetic stimuli, and for the role of α-receptors.