Notes

Outline

Push-Pull A theoretical construct for the microcirculation William J. Ennis D.O.,MBA,FACOS Medical Director, Comprehensive Wound and Disease management center, St. James Hospital Clinical Professor Surgery, Midwestern University President Elect AAWC

Disclosures Medical Advisor, National Medical Solutions Consultant Celleration Inc

Overview Microcirculation Anatomy Physiology Organ level clinical examples Shock, Cardiac, Liver Diagnostic options Wound care applications Chronic Venous insufficiency VLU Microcirulatory treatment options Limb ischemia Microcirculatory changes Revascularization No reflow Capillary recruitment techniques Push pull

Amp rates unchanging AM J Pub Health 1999 :89;1221-1227 1980’s with establishment of certification in PV surg and distal bypass the numbers of amps dropped In the early 1990’s with interventions the numbers further lowered 1995/96 rate per 100,000 slightly up from 1993 and higher than the past 18 year mean J Vasc Surg. 2005 Jul;42(1):81-7  Physician supply, treatment, and amputation rates for peripheral arterial disease. Ho V, Wirthlin D, Yun H, Allison J. Insert healthy people 2000,2010

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Microcirculation Anatomy 85% thermal shunting, 15% nutritive basal A vital organ of the CV system whose function it is to ensure adequate delivery of oxygen by blood to various tissue cells

Microcirculation Tc02 monitoring Laser doppler imaging P-31 NMR spectroscopy PET scan Orthogonal polarization spectroscopy SDF – side stream dark field

Microcirculation Tc02 monitoring Laser doppler imaging

ATP/PCr analysis in wounds Ennis, Driscoll, Meneses Wounds 1994;6(5):166-173

PET Scan Schrey et al J Plast Recon 2006;59:158-165 Functional evaluation of microvascular free flap with PET scan Flap to muscle blood flow ratio determined the success of flap

University of Western Ontario IVVM Indiana Center Biological Microscopy Scott JR, Potter RF Small intestine post capillary venule following hindlimb Ischemia/Reperfusion

SDF  imaging Elbers et al Critical Care 2006;10:221 Classifying microcirculatory abnormalities in distributive shock

Perfusion within this system is based upon Arterial oxygen saturation Blood viscosity RBC deformability Shunting Vasodilation Vasoconstriction Diffusion constant of gases Distance from cell to nearest vessel

Crit care med 2004;32:1825-1831 Sakr et al 49 patients in ICU with septic shock Sublingual microcirculation studied with OPS, day of sepsis and daily until recovered or death 26 patients survived, 20 died At onset of shock survivors and non had similar vascular density and percentage of perfused vessels Overall perfusion improved in survivors over time p<0.05 Patients dying after the resolution of shock had a lower percentage of perfused vessels

Clinical examples Clinical Examples Distributive Shock Gut Liver Wound applications CVI Ischemic wounds

Microcirculation J Vasc Surg 2002;35:501-5 Arora et al (LoGerfo) Impaired vasodilation in diabetic neuropathic lower extremities improves but is not completely reversed with successful bypass grafting.(laser doppler trial) Post revasc diabetic patients may therefore still be at risk for foot ulceration and may fail to heal the ulcer despite adequate correction of macrovascular flow

No Reflow phenomenon Introduced 1967 Ames Cerebral ischemia in rabbits Occlusion of vessel greater than 2 minutes resulted in failure to completely reperfuse when vessel unclamped Kloner 1974 reproduced in dogs with histological findings Swollen endothelium, and dysfunction Correlated to area of necrosis

Microcirculation J Vasc Surg 2002;35:501-5 Arora et al (LoGerfo) Impaired vasodilation in diabetic neuropathic lower extremities improves but is not completely reversed with successful bypass grafting.(laser doppler trial) Post revasc diabetic patients may therefore still be at risk for foot ulceration and may fail to heal the ulcer despite adequate correction of macrovascular flow

Clinical Example of Using All Techniques for Micro Flow J vasc Surg 1999 30(1) 114-121 111 patients with NRVD ABI<0.35 and ankle pressure < 50 Categorized based on the Tcpo2 , laser doppler and capillary microscopy great toe

Clinical Example of Using All Techniques for Micro Flow

Stunned Wound

No Reflow phenomenon Introduced 1967 Ames Cerebral ischemia in rabbits Occlusion of vessel greater than 2 minutes resulted in failure to completely reperfuse when vessel unclamped Kloner 1974 reproduced in dogs with histological findings Swollen endothelium, and dysfunction Correlated to area of necrosis

No Reflow phenomenon 25-35% of capillaries are perfused at rest Loss of capillary recruitment Pathophysiology Microvascular obstruction Microthromboemboli Spasm Leukocyte entrapment Reperfusion Injury Platelet activation Neutrophil integrin expression Oxygen free radical release

Diabetic Med 2005;22(4):460-465 Caselli et al 23pts with successful revasc, 20 w/o retro Tcp02 1,7,14,21,28 days post revasc Successful revasc pts had increases immediately with a peak at 4 weeks Total of 75% of cases >30 at 4 weeks Unsuccessful revasc, small initial rise but stable for 4 weeks NOTE: Possible reason to wait 4 weeks for definitive debridement in non-septic cases

J Cardiovasc Pharmacol Ther 2004;9(3):163-172 Reffelmann and Kloner Review article Tissue perfusion after perfusion-reperfusion injury remains dysfunctional in cardiac tissue for 4 weeks 4 week analysis of tissue perfusion is predictive of scar thickness, infarct healing, and infarct expansion

Treatment options

Treatment options

Mouse Study – Blood Flow Effects New Blood Vessel Growth

Ennis WJ, Valdes W, Gainer M, Meneses P. Adv Skin and wound care 2006;

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Proteomics