Orthostatic hypotension is associated with impaired cardiac structure and function after spinal cord injury

Abstract

Heart disease is a primary cause of death after spinal cord injury (SCI). A 20 mmHg or more reduction in systolic blood pressure (BP) when assuming the upright posture is termed orthostatic hypotension (OH). Epidemiological data in the general population established a causal relationship between OH and heart disease. Orthostatic hypotension and heart disease are widespread after SCI however, it is unknown if the severity of OH after SCI is associated with cardiac structure or function and markers of cardiac health. We aimed to understand this relationship combining an interventional rodent study and a cross-sectional clinical study, using gold standard invasive techniques and cardiac-optimized magnetic resonance imaging, respectively. We hypothesized that after SCI, OH severity would be associated with reduced cardiac structure and function as well as poorer markers of cardiac health. Twenty-one wistar rats underwent a complete transection at the T3 spinal segment. One week later, half of these animals were exposed to five one-minute intervals of simulated OH daily for eight weeks using a custom lower body negative pressure chamber (n=10; Fig. 1A). Nine weeks post-SCI, invasive pressure-volume catheterization and inferior vena cava occlusion were performed on both groups. Daily exposure to OH impaired left ventricle (LV) structure and function in rats with SCI as evidenced by reduced stroke volume (SV), cardiac output (Q), and end-systolic elastance (Ees), along with increased ventricular-vascular coupling (VVC) and arterial elastance (Ea; Fig. 1B). Guided by these interventional preclinical results, we next cross-sectionally tested this association in a group of eight individuals with motor-complete chronic SCI using 3-Tesla cardiac-optimized magnetic resonance imaging (Fig. 1C), 24-hour ambulatory blood pressure monitoring (Fig. 1D), and orthostatic tilt-table testing at 60 degrees following clinical guidelines (Fig. 1E). More severe OH was associated with impaired cardiac structure and poorer markers of cardiac health, indicated by increased LV mass, increased left atrial volume, and increased troponin T (Fig. 1F). Our translational research, using both interventional preclinical and cross-sectional clinical assessments, indicates that OH after SCI is associated with impaired cardiac structure and function as well as poorer markers of cardiac health. The next step is to test if mitigating OH after SCI prevents this decline.