Why less is often more: Individualizing shear rate therapy for systemic atherosclerosis.

Soubh et al.1 have recently reported in Acta Physiologica how a non-invasive, individualized therapeutic regimen (individual shear rate therapy, ISRT) significantly improves tolerability, safety, and effectiveness of external pulsation therapy (EPT) in patients with peripheral artery disease (lower extremity atherosclerotic disease, LEAD). What else is new, you might ask. Is not external counterpulsation, that is, the ECG-triggered repeated sequential inflation of pneumatic pressure cuffs around the legs to increase coronary blood flow during diastole,2 a really old hat? And am I still reading a general physiology journal? If so, bear with us. EPT alleviates angina and improves both exercise tolerance and peak oxygen consumption in chronic myocardial ischemia beyond acute hemodynamic effects2, 3 through flow-mediated NO release, improved endothelial function4 and positive outward remodeling of collateral arteries. Side effects, however, are plenty, given that conventional high-pressure EPT machines, called enhanced external counterpulsation (EECP) devices, elicit cuff pressures of 250–300 mmHG. Also, evidence of potential positive effects of EECP in non-cardiac vascular beds is patchy at best, as for example EECP-impaired perfusion of the lower limbs rules out all patients in whom vascular occlusive disease systemically affects the lower extremities as well as the myocardium. Soubh et al have, in 18 pilot patients, addressed that issue: ISRT (= individually tailored low-pressure EPT) uses subsystolic cuff pressures, which significantly increased sO2, relative hemoglobin amount (rHb) and blood flow in the targeted microcirculation during and beyond treatment, while typical EECP –induced subjective discomfort and parameters of pressure – induced organ damage did not occur with ISRT. When first introduced, EECP was groundbreaking: a non-invasive alternative to the intra-aortic balloon pump. Equipment, material, and training are accessible outside of specialized centers, adding to its therapeutic potential. However, it might be time to move on from its one-size-fits-all concept, and this is where general physiology steps into the picture. Interestingly, MUST-EECP2 had shown effects on exercise tolerance in a low-pressure (“control”) group. At the time, one might have overheard the occasional suspicion that the daily walk to the EECP laboratory for 7 weeks is what all of these patients indeed benefitted from. Nowadays ISRT, in contrast to EECP, is able to tailor therapeutic EPT to individual patients by adjusting cuff inflation pressure for maximal flow enhancement in the targeted vascular bed.7 Revascularization by EPT is unlikely to be achieved by a counterpulsating, pressure-dependent opening of collaterals, as had been assumed earlier (think: arterial autoregulation), but rather a stimulation of flow-dependent positive endothelial effects, and, ultimately, outward remodeling of preexistent collateral arteries, arteriogenesis.5 Thus, ISRT is a promising approach toward a safe and effective option for patients with myocardial ischemia and atherosclerotic comorbidities in other vascular beds. Personalized precision medicine needs interdisciplinarity. To this end, at Acta Physiologica, we are more than happy to provide a platform for the open interdisciplinary exchange of ideas and concepts, from the laboratory to the bedside and vice versa, as exemplified in.1, 6 Once clinician scientists and general physiologists cooperate closely, good things happen: Soubh et al.1 highlights the direct and immediate importance of general physiology for fine-tuning modern and excellent patient care. None.