{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T15:44:18Z","timestamp":1792424658303,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Critical closing pressure (CCP) and the vascular waterfall have long been used to explain perfusion failure in shock, yet their physiological meaning has been inconsistently interpreted. CCP is frequently treated as a continuous downstream pressure and inserted into formulas such as mean arterial pressure (MAP) \u2212 CCP, implying that a collapse threshold behaves like an opposing pressure even when vessels remain open. Drawing on classical vascular mechanics, whole-bed flow studies, microvascular models, and contemporary clinical physiology, we show that this interpretation is incorrect. Tone-dependent arteriolar collapse does not behave as a Starling resistor: CCP is a threshold at which smooth-muscle tension exceeds intraluminal pressure and vessels close, not a pressure governing flow in patent vessels. Perfusion becomes heterogeneous because different vascular beds reach their collapse thresholds at different pressures (via excessive tone, extrinsic compression, or profound hypotension), disconnecting macro-haemodynamics from microcirculatory flow. This explains why systemic variables such as MAP and systemic vascular resistance (SVR) may appear adequate even while tissues are under-perfused, a phenomenon now termed haemodynamic incoherence. Reframing CCP as a binary collapse threshold resolves longstanding contradictions in the literature, clarifies why MAP-centred targets often fail, and unifies the behaviour of shock states within a four-interface model of circulatory coupling. Therapeutically, the aim is not to \u201crestore a waterfall\u201d but to reopen closed vascular territories by lowering excessive tone, relieving external pressure, or raising truly low arterial inflow. This mechanistic reinterpretation provides a more coherent, physiologically grounded approach to personalised perfusion management in critical illness.<\/jats:p>","DOI":"10.3390\/jpm16020078","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:03:29Z","timestamp":1770113009000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Arteriolar Collapse and Haemodynamic Incoherence in Shock: Rethinking Critical Closing Pressure"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6665-1514","authenticated-orcid":false,"given":"Ashley","family":"Miller","sequence":"first","affiliation":[{"name":"Shrewsbury and Telford Hospitals, Shrewsbury SY3 8XQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4425-9212","authenticated-orcid":false,"given":"Philippe","family":"Rola","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Santa Cabrini Hospital, CIUSSS EMTL, University of Montreal, Montreal, QC H1T1P7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7105-3885","authenticated-orcid":false,"given":"Rory","family":"Spiegel","sequence":"additional","affiliation":[{"name":"Departments of Critical Care and Emergency Medicine, Medstar Washington Hospital Center, Washington, DC 20010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2331-5107","authenticated-orcid":false,"given":"Korbin","family":"Haycock","sequence":"additional","affiliation":[{"name":"Loma Linda University Medical Center, Loma Linda, CA 92354, USA"},{"name":"Desert Regional Medical Center, Palm Springs, CA 92262, USA"},{"name":"Departments of Emergency Medicine, Riverside University Health System Medical System, Moreno Valley, CA 92555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2305","DOI":"10.1097\/CCM.0000000000006805","article-title":"Assessment of Tissue Perfusion Pressure in Patients With Septic Shock: Beyond Mean Arterial Pressure","volume":"53","author":"Sanchez","year":"2025","journal-title":"Crit. Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13613-015-0085-5","article-title":"Personalizing blood pressure management in septic shock","volume":"5","author":"Kato","year":"2015","journal-title":"Ann. Intensive Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40635-023-00539-x","article-title":"Effect of norepinephrine on the vascular waterfall and tissue perfusion in vasoplegic hypotensive patients: A prospective, observational, applied physiology study in cardiac surgery","volume":"11","author":"Andrei","year":"2023","journal-title":"Intensive Care Med. Exp."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40560-021-00587-z","article-title":"Esmolol response in septic shock patients in relation to vascular waterfall phenomenon measured by critical closure pressure and mean systemic filling pressure: A prospective observational study","volume":"10","author":"Liu","year":"2022","journal-title":"J. Intensive Care"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1186\/cc14726","article-title":"Hemodynamic coherence and the rationale for monitoring the microcirculation","volume":"19","author":"Ince","year":"2015","journal-title":"Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1097\/SHK.0000000000002507","article-title":"Understanding hemodynamic incoherence: Mechanisms, phenotypes, and implications for treatment","volume":"63","author":"Huang","year":"2025","journal-title":"Shock"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rola, P., Kattan, E., Siuba, M.T., Haycock, K., Crager, S., Spiegel, R., Hockstein, M., Bhardwaj, V., Miller, A., and Kenny, J.E. (2025). Point of View: A Holistic Four-Interface Conceptual Model for Personalizing Shock Resuscitation. J. Pers. Med., 15.","DOI":"10.20944\/preprints202503.1988.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1111\/aas.12581","article-title":"Microcirculatory dysfunction and tissue oxygenation in critical illness","volume":"59","author":"Granfeldt","year":"2015","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1161\/01.RES.59.5.483","article-title":"Autoregulation of blood flow","volume":"59","author":"Johnson","year":"1986","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1152\/ajplegacy.1955.180.3.463","article-title":"Effect of mean circulatory filling pressure and other peripheral circulatory factors on cardiac output","volume":"180","author":"Guyton","year":"1955","journal-title":"Am. J. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10877-008-9147-7","article-title":"Therapeutic control of the circulation","volume":"22","author":"Parkin","year":"2008","journal-title":"J. Clin. Monit. Comput."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s40635-025-00828-7","article-title":"Venous congestion from a vascular waterfall perspective: Reframing congestion as a dynamic Starling resistor phenomenon","volume":"13","author":"Castro","year":"2025","journal-title":"Intensive Care Med. Exp."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1152\/advan.00074.2010","article-title":"Local control of blood flow","volume":"35","author":"Clifford","year":"2011","journal-title":"Adv. Physiol. Educ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1213\/ANE.0b013e318247fa44","article-title":"Determination of vascular waterfall phenomenon by bedside measurement of mean systemic filling pressure and critical closing pressure in the intensive care unit","volume":"114","author":"Maas","year":"2012","journal-title":"Anesth. Analg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1097\/ALN.0b013e3181942c99","article-title":"Critical closing pressure as the arterial downstream pressure with the heart beating and during circulatory arrest","volume":"110","year":"2009","journal-title":"Anesthesiology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1152\/jappl.1963.18.5.924","article-title":"Hemodynamics of Collapsible Vessels with Tone: The Vascular Waterfall","volume":"18","author":"Permutt","year":"1963","journal-title":"J. Appl. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1152\/ajplegacy.1951.164.2.330","article-title":"Fundamental instability of the small blood vessels and critical closing pressures in vascular beds","volume":"164","author":"Nichol","year":"1951","journal-title":"Am. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1152\/ajplegacy.1951.164.2.319","article-title":"On the physical equilibrium of small blood vessels","volume":"164","author":"Burton","year":"1951","journal-title":"Am. J. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s12028-023-01691-8","article-title":"Critical Closing Pressure and Cerebrovascular Resistance Responses to Intracranial Pressure Variations in Neurocritical Patients","volume":"39","author":"Brasil","year":"2023","journal-title":"Neurocrit. Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13054-024-04912-4","article-title":"Significance of critical closing pressures (starling resistors) in arterial circulation","volume":"28","author":"Pinsky","year":"2024","journal-title":"Crit. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1038\/s41591-023-02474-6","article-title":"Tissue perfusion pressure enables continuous hemodynamic evaluation and risk prediction in the intensive care unit","volume":"29","author":"Chandrasekhar","year":"2023","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1113\/jphysiol.1914.sp001669","article-title":"On the mechanical factors which determine the output of the ventricles","volume":"48","author":"Patterson","year":"1914","journal-title":"J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1152\/jappl.1991.70.1.169","article-title":"Flow redistribution during progressive hemorrhage is a determinant of critical O2 delivery","volume":"70","author":"Schlichtig","year":"1991","journal-title":"J. Appl. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/ki.1986.270","article-title":"The effects of angiotensin II and norepinephrine on afferent arterioles in the rat","volume":"30","author":"Wilson","year":"1986","journal-title":"Kidney Int."},{"key":"ref_25","first-page":"F526","article-title":"Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels","volume":"244","author":"Edwards","year":"1983","journal-title":"Am. J. Physiol."},{"key":"ref_26","first-page":"F274","article-title":"Renal microvascular effects of vasopressin and vasopressin antagonists","volume":"256","author":"Edwards","year":"1989","journal-title":"Am. J. Physiol."},{"key":"ref_27","first-page":"285","article-title":"Effects of renal lymphatic occlusion and venous constriction on renal function","volume":"78","author":"Stolarczyk","year":"1975","journal-title":"Am. J. Pathol."},{"key":"ref_28","unstructured":"The ANDROMEDA-SHOCK-2 Investigators for the ANDROMEDA Research Network, Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), and Latin American Intensive Care Network (LIVEN) (2025). Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial. JAMA, 334, 1988\u20131999."}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/2\/78\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:19:50Z","timestamp":1770113990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/2\/78"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,1]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jpm16020078"],"URL":"https:\/\/doi.org\/10.3390\/jpm16020078","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,1]]}}}