Metaboreflex-mediated hemodynamic abnormalities in individuals with coronary artery disease without overt signs or symptoms of heart failure

Abstract

This study was devised to investigate the effect of coronary artery disease (CAD) without overt signs of heart failure on the cardiovascular responses to muscle metaboreflex activation. We hypothesized that any CAD-induced preclinical systolic and/or diastolic dysfunction could impair hemodynamic response to the metaboreflex test. Twelve men diagnosed with CAD without any sign or symptoms of heart failure and 11 age-matched healthy control (CTL) subjects participated in the study. Subjects performed a postexercise muscle ischemia (PEMI) test to activate the metaboreflex. They also performed a control exercise recovery test to compare data from the PEMI test. The main results were that the CAD group reached a similar mean arterial blood pressure response as the CTL group during PEMI. However, the mechanism by which this response was achieved was different between groups. In particular, CAD achieved the target mean arterial blood pressure by increasing systemic vascular resistance (ϩ383.8 Ϯ 256.6 vs. ϩ91.2 Ϯ 293.5 dyn•s Ϫ1 •cm Ϫ5 for the CAD and CTL groups, respectively), the CTL group by increasing cardiac preload (Ϫ0.92 Ϯ 8.53 vs. 5.34 Ϯ 4.29 ml in end-diastolic volume for the CAD and CTL groups, respectively), which led to an enhanced stroke volume and cardiac output. Furthermore, the ventricular filling rate response was higher in the CTL group than in the CAD group during PEMI (P Ͻ 0.05 for all comparisons). This study confirms that diastolic function is pivotal for normal hemodynamics during the metaboreflex. Moreover, it provides evidence that early signs of diastolic impairment attributable to CAD can be detected by the metaboreflex test. NEW & NOTEWORTHY Individuals suffering from coronary artery disease without overt signs of heart failure may show early signs of diastolic dysfunction, which can be detected by the metaboreflex test. During the metaboreflex, these subjects show impaired preload and stroke volume responses and exaggerated vasoconstriction compared with controls.

A brief bout of exercise in hypoxia reduces ventricular filling rate and stroke volume response during muscle metaboreflex activation

“…It seems well ascertained by human as well as by animal studies that in healthy individuals, the metaboreflex activation enhances cardiac performance and pre-load thereby sustaining SV (Bastos et al 2000 ; Crisafulli et al 2008 ; Crisafulli et al 2009 ; Crisafulli et al 2013 ; Crisafulli 2017 ; Nobrega et al 2014 ; O'Leary and Augustyniak 1998 ; Sheriff et al 1998 ; Shoemaker et al 2005 ). Actually, pathological impairment in one of these hemodynamic modulators (as happens for example in heart failure, spinal cord injury, or diastolic dysfunction) blunts the SV response to metaboreflex, but usually the MAP is well preserved (Crisafulli 2017 ; Crisafulli et al 2009 ; Milia et al 2015 ; Magnani et al 2018 ; Roberto et al 2017 ; Sala-Mercado et al 2006 ).…”

“…Indeed, the compression applied after exercise induces a temporary arterial and venous occlusion that traps muscle metabolites produced during exercise thereby stimulating the metaboreflex and, at the same time, excluding the influence of mechanoreflex and central command (Crisafulli et al 2008 ; Scott et al 2002 ). The PEMI manoeuvre has been demonstrated to be effective in evoking changes in cardiac preload, afterload, and inotropism in healthy humans as well as in patients suffering from various cardiovascular diseases (Crisafulli 2017 ; Magnani et al 2018 ; Marongiu et al 2013 ; Milia et al 2015 ; Mulliri et al 2016 ; Roberto et al 2017 ).…”

Hemodynamic abnormalities during muscle metaboreflex activation in patients with type 2 diabetes mellitus

“…This procedure has been previously used in our laboratory during similar investigations aiming to study hemodynamics during metaboreflex in normal subjects and in various cardiovascular and metabolic diseases. A detailed description of the data acquisition and processing methods are present in these previous papers (7,10,29,34,35,49). Briefly, NCCOM 3-derived analog traces of electrocardiogram, Z0, and Z0 first derivative were stored, and SV was calculated offline along with the pre-ejection period (PEP) and left ventricular ejection time (VET) (31,55).…”

“…Furthermore, for each parameter, the difference between values of the PEMI and the CER tests during the third minute of recovery (i.e., when a steadystate in parameters was supposed to be reached) was calculated. This allowed us to assess responses because of metaboreflex activity (11,29,34). The difference between groups in parameters' responses was carried out by unpaired t-test.…”

“…Conversely, when cardiac preload and/or inotropism cannot be enhanced, then SV and CO cannot properly increase in response to PEMI. This, in turn, is accompanied by exaggerated SVR increments (7,8,10,11,29,34,35,49). Moreover, it has been observed that in clinical conditions characterized by excessive sympathetic tone, such as hypertension, heart failure, obesity, and metabolic syndrome, there is a pronounced arteriolar constriction that causes exaggerated SVR increments, thereby leading to ventricular afterload elevation in response to the metaboreflex (6,13,17,35,45).…”