Fundamental hemodynamic mechanisms mediating the response to myocardial ischemia in conscious paraplegic mice: cardiac output versus peripheral resistance

Abstract

Autonomic dysfunction, a relative sedentary lifestyle, a reduced muscle mass and increased adiposity leads to metabolic abnormalities that accelerate the development of coronary artery disease (CAD) in individuals living with spinal cord injury (SCI). An untoward cardiac incident is related to the degree of CAD, suggesting that the occurrence of a significant cardiac event is significantly higher for individuals with SCI Thus, understanding the fundamental hemodynamic mechanisms mediating the response to myocardial ischemia has the potential to positively impact individuals and families living with SCI Accordingly, we systematically investigated if thoracic level 5 spinal cord transection (T₅X; paraplegia) alters the arterial blood pressure response to coronary artery occlusion and if the different arterial blood pressure responses to coronary artery occlusion between intact and paraplegic mice are mediated by changes in cardiac output and or systemic peripheral resistance and whether differences in cardiac output are caused by changes in heart rate and or stroke volume. To achieve this goal, the tolerance to 3 min of coronary artery occlusion was determined in conscious intact and paraplegic mice. Paraplegic mice had an impaired ability to maintain arterial blood pressure during coronary artery occlusion as arterial pressure fell to near lethal levels by 1.38 ± 0.64 min. The lower arterial pressure was mediated by a lower cardiac output as systemic peripheral resistance was elevated in paraplegic mice. The lower cardiac output was mediated by a reduced heart rate and stroke volume. These results indicate that in paraplegic mice, the arterial pressure response to coronary artery occlusion is hemodynamically mediated primarily by cardiac output which is determined by heart rate and stroke volume.

Keywords: Coronary artery disease; myocardial ischemia; spinal reflex.

Figure 1

One second original recordings of cardiac output, arterial pressure, and the electrocardiogram for one intact (panel A) and one paraplegic (panel B) mouse are presented. Coronary artery occlusion significantly reduced arterial pressure in paraplegic mice. The reduced arterial pressure was mediated by a reduced cardiac output. None of the T₅X mice tolerated 3 min of occlusion. In this example, the duration of the occlusion for the T₅X mouse was 1.6 min.

Figure 2

Arterial pressure (Panel A), cardiac output (Panel B), systemic peripheral resistance (Panel C), heart rate (Panel D), and stroke volume (Panel E) in conscious intact and paraplegic mice are presented. Preocclusion arterial pressure, cardiac output, and stroke volume were significantly lower while heart rate was significantly higher in T₅X mice. There was no difference in preocclusion systemic peripheral resistance. The lower preocclusion arterial pressure in the mice with paraplegia was the result of a lower cardiac output with no contribution of systemic peripheral resistance. Since preocclusion heart rate was significantly elevated in the mice with paraplegia, the lower preocclusion cardiac output was the result of a lower stroke volume. Moreover, T₅X mice had an impaired ability to maintain arterial blood pressure during coronary artery occlusion as arterial pressure fell to near lethal levels by 1.38 ± 0.64 min. The impaired ability to maintain arterial pressure during coronary artery occlusion in paraplegic mice was mediated by a lower cardiac output as peripheral resistance was elevated. The lower cardiac output was mediated by a reduced stroke volume and heart rate. *P ≤ 0.05, T5X versus Intact #P ≤ 0.05, T5X; Preocclusion versus 1 min, 1.38 min release, 30 min reperfusion +P ≤ 0.05, Intact; Preocclusion versus 1 min, 2 min, 3 min, 30 min reperfusion

Figure 3

Changes in arterial pressure (Panel A), cardiac output (Panel B), systemic peripheral resistance (Panel C), heart rate (Panel D), and stroke volume (Panel E) from control in conscious intact and paraplegic mice are presented. Paraplegic mice had an impaired ability to maintain arterial blood pressure during coronary artery occlusion as the change in arterial pressure was greater in paraplegic mice (Panel A). The lower arterial pressure was mediated by a larger change in cardiac output (Panel B) as systemic peripheral resistance was elevated in paraplegic mice (Panel C). The lower cardiac output was mediated by a reduced heart rate (Panel D). *P ≤ 0.05, T5X versus Intact

Figure 4

Ventricular sections from one intact and paraplegic mouse are shown. The only collagen (i.e., blue stain, documenting tissue injury) shows placement of the coronary artery occluder. Thus, little tissue damage occurs during the ischemia.