title: Cardiac Consequences of Autonomic Dysreflexia in Spinal Cord Injury.
abstract: Autonomic dysreflexia (AD), which describes episodic hypertension, is highly prevalent in people with spinal cord injury (SCI). In non-SCI, primary hypertension depresses cardiac contractile reserve via β-adrenergic mechanisms. In this study, we investigated whether AD contributes to the impairment in cardiac contractile function that accompanies SCI. We induced SCI in rodents and stratified them into sham, SCI, or SCI plus repetitive induction of AD. At 6-week post-SCI, we assessed cardiac function using in vivo (speckle-tracking echocardiography), ex vivo (working heart), and molecular approaches (Western blot). We also provide unique translational insight by comparing the relationship between the number of daily AD events and cardiac function in 14 individuals with cervical SCI. We found SCI and SCI plus repetitive induction of AD exhibited a reduction in left ventricular dimensions at 6-week post-SCI versus preinjury (P<0.049). Compared with sham, SCI exhibited a reduction in peak radial strain along with a down and rightward shift in the Starling curve (P<0.037), both of which were further depressed in SCI plus repetitive induction of AD (P<0.042). In response to β-adrenergic stimulation, SCI plus repetitive induction of AD exhibited an attenuated increase in contractile indices (P<0.001), despite no differences in β-receptor expression within the left ventricle. Our clinical data confirm our experimental findings by demonstrating significant associations between the number of daily AD events and markers of systolic and diastolic function along with left ventricular mechanics. Here, we provide the first evidence from a translational perspective that AD exerts insidious effects on cardiac function in rodents and humans with SCI.
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Christopher R
authors.initials: CR
authors.lastname: West
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Squair
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Laura
authors.initials: L
authors.lastname: McCracken
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Katharine D
authors.initials: KD
authors.lastname: Currie
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Rishi
authors.initials: R
authors.lastname: Somvanshi
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Violet
authors.initials: V
authors.lastname: Yuen
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Phillips
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K).
authors.forename: John H
authors.initials: JH
authors.lastname: McNeill
authors.affiliation: From the International Collaboration on Repair Discoveries (C.R.W., J.W.S., L.M., K.D.C., A.A.P., A.V.K), School of Kinesiology, Faculty of Education (C.R.W., L.M.), MD-PhD Training Program, Faculty of Medicine (J.W.S.), Faculty of Pharmaceutical Sciences (R.S., V.Y., U.K., J.H.M.), and Faculty of Medicine, Division of Physical Medicine and Rehabilitation (A.V.K), University of British Columbia, Vancouver, Canada; Faculty of Kinesiology and Physical Education, University of Toronto, ON, Canada (K.D.C.); and GF Strong Rehabilitation Centre, Vancouver Coastal Health, BC, Canada (A.V.K). krassioukov@icord.org.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Krassioukov
mesh_terms: D000818:Animals; D020211:Autonomic Dysreflexia / Q000150:complications* / Q000503:physiopathology; D018660:Blood Pressure Monitoring, Ambulatory; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D000075222:Essential Hypertension; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D015999:Multivariate Analysis; D009200:Myocardial Contraction / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012044:Regression Analysis; D018570:Risk Assessment; D012494:Sampling Studies; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology*
keywords: cardiovascular diseases; echocardiography; hypertension; spinal cord injuries; systole