Muscle metaboreflex-induced coronary vasoconstriction functionally limits increases in ventricular contractility

Abstract

Muscle metaboreflex activation during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility, and afterload. This increase in cardiac work should cause coronary metabolic vasodilation. However, little if any coronary vasodilation is observed due to concomitant sympathetically induced coronary vasoconstriction. The purpose of the present study is to determine whether the restraint of coronary vasodilation functionally limits increases in left ventricular contractility. Using chronically instrumented, conscious dogs (n = 9), we measured mean arterial pressure, cardiac output, and circumflex blood flow and calculated coronary vascular conductance, maximal derivative of ventricular pressure (dp/dt(max)), and preload recruitable stroke work (PRSW) at rest and during mild exercise (2 mph) before and during activation of the muscle metaboreflex. Experiments were repeated after systemic alpha(1)-adrenergic blockade ( approximately 50 microg/kg prazosin). During prazosin administration, we observed significantly greater increases in coronary vascular conductance (0.64 + or - 0.06 vs. 0.46 + or - 0.03 ml x min(-1) x mmHg(-1); P < 0.05), circumflex blood flow (77.9 + or - 6.6 vs. 63.0 + or - 4.5 ml/min; P < 0.05), cardiac output (7.38 + or - 0.52 vs. 6.02 + or - 0.42 l/min; P < 0.05), dP/dt(max) (5,449 + or - 339 vs. 3,888 + or - 243 mmHg/s; P < 0.05), and PRSW (160.1 + or - 10.3 vs. 183.8 + or - 9.2 erg.10(3)/ml; P < 0.05) with metaboreflex activation vs. those seen in control experiments. We conclude that the sympathetic restraint of coronary vasodilation functionally limits further reflex increases in left ventricular contractility.

Fig. 1.

A: example of pressure-volume loop during preload reductions, illustrating stroke work of a single loop (shaded) and the end-diastolic volume point (●) for each loop. B: example of how the end-diastolic points and corresponding stroke work for each loop is used to illustrate preload recruitable stroke work (PRSW) and how it can be used to assess contractility.

Fig. 2.

Hemodynamic responses. Shown are mean arterial pressure (MAP), heart rate (HR) in beats/min (bpm), left ventricular volumes (LVVs), cardiac output (CO), and nonischemic vascular conductance (NIVC) responses during rest, mild exercise (Ex), and mild exercise with muscle metaboreflex activation (Ex+MMA) settings in control (solid bars) and α₁-adrenergic blockade conditions (hatched bars). All parameters showed significance across workload settings, as well as significance between control and prazosin conditions (P < 0.05), with the exception of stroke volume and left-ventricular end-systolic volume (which were only significant across workload settings). All parameters had a significant interaction between the 2 independent variables, with the exception of left ventricular end-systolic volume. *Between 2 bars, signifies a significant pair-wise comparison (P < 0.05). †Significant increase from the previous setting. ♣Above a specific setting, signifies a significant pair-wise comparison in left ventricle stroke volume (P < 0.05). ‡Significant increase in left ventricular end-diastolic volume. #Significant increase in stoke volume from the previous workload (P < 0.05). *Next to bracket, indicates a significance between left ventricular end-systolic volume across workloads but not between control and α₁-adrenergic blockade conditions.

Fig. 3.

Left ventricular hemodynamic and function responses. Shown are coronary blood flow (CBF), coronary vascular conductance (CVC), maximal rate of left ventricular pressure change (dP/dt_max), and PRSW during rest, EX, and Ex+MMA settings, in control (solid bars) and α₁-adrenergic blockade conditions (hatched bars). All parameters showed significance across workload settings, as well as significance between control and prazosin conditions (P < 0.05). All parameters had a significant interaction between the 2 independent variables. *Above a specific setting, signifies a significant pair-wise comparison (P < 0.05). †Significant increase from the previous setting (P < 0.05).

Fig. 4.

CVC plotted as a function of cardiac power. The broken regression line represents the average relationship between CVC and cardiac power in control, whereas the solid regression line represents the corresponding average relationship during α₁-adrenergic blockade. ♦, Averaged values in control condition. ◊, Averaged values during α₁-adrenergic blockade. Bracket and asterisk signify the significant difference between the 2 slopes (P < 0.05).

Fig. 5.

Contractility indicated by PRSW with respect to CBF. As no significant difference between control and α₁-adrenergic blockade was found (P > 0.05), a single relationship is represented by a single line. ●, Averaged values in controls. ○, Averaged values during α₁-adrenergic blockade.