We have already reported that a decrease in blood pressure during HUT was due to a decrease in CO, i.e. reduced SV, in CAD patients just after the surgery, because a decrease in SV and the decreased blood pressure was exacerbated even HR response was improved in nine patients [3]. In the present study, we followed-up cardiovascular responses during the HUT test in the patients 1.3–1.8 years after undergoing CABG. The main findings of the present study in six of the nine patients, who have completed ~ 1.5 years after measurements, were: 1) the HUT-related decrease in MAP at discharge was restored over 1 year after CABG even 2) CO tended to be still lower due to lower SV, contrary to our expectations, and 3) the present design is feasible in a clinical site but sample size was limited only in a single center.
To explain the mechanisms of the present phenomena, pressor response via sympathetic nerve activity was improved, in the other word, baroreflex sensitivity was increased, even the influences of medication status, such as suggested hypovolemia induced by some of medications, and possibly less physical activity after discharge would affect the control of blood pressure negatively. However, as we did not assess blood volume, physical activity after discharge, and baroreflex sensitivity directly.
The present medication status possibly influenced MAP control not only directly but also indirectly via reduced SV. It has been well-known that antihypertensives are considered to be a cause of orthostatic hypotension; e.g. diuretics induce a predispose of volume depletion, b-blockers show negative inotropic and chronotropic effects, nitrates have vasodilating effects via nitric oxide (NO) release and vascular smooth muscle relaxation, and predominantly the venous district, resulting in reducing the venous return to the heart [9, 10, 19]. As shown in Table 2, nitrates and diuretics were prescribed right after surgery and these medicines would induce the reduction of MAP just after surgery partially. Dietary nitrates have been shown to decrease blood pressure via enhanced vascular conductance because nitrate can be reduced to NO, which is a strong vasodilator [20], through the nitrate-nitrite-NO pathway [21]. Diuretics reduce body fluid volume, resulting in a decrease in venous return to the heart [22]. Taking b-blockers could lower CO after surgery [23], as only two patients took it before surgery and all ones did after surgery (Table 2). As all patients did not undergo any test that HR elevates over approximately 100 beats/min in the present measurement and EF remained unchanged before and during HUT, the contribution of taking b-blockers on blood pressure control during HUT might not be so high [24]. However, combined treatment of diuretics and b-blockers lower blood pressure more than one of each treatment, because b-blockers suppress an increase in plasma renin activity and then attenuate potassium excretion, resulting in strengthening the effects of diuretics indirectly [25]. Therefore, combined enhanced vasodilation via nitrates and hypovolemia by diuretics and/ or b-blockers might induce a further reduction of MAP just after surgery.
The medication statuses were changed over one year after surgery; only one patient and three patients took diuretics and nitrates, respectively, while six patients took b-blockers (Table 2). The influences of nitrates and diuretics on blood pressure control would be attenuated in the patients who ceased taking the above medicines. On the other hand, SV was still lower than that before surgery over one year after surgery as shown in Table 4 and SV could be an index of blood volume, which is directly related with venous return to the heart [26]. The fact that SV remained lower ~ 1.5 years after surgery suggest that hypovolemia would be prolonged although we did not assess blood volume directly [24]. As prescription of b-blockers was alive over a year after the surgery and antihypertensive effects of b-blockers for long-term were equivalent that for the acute phase [27], the medication status could induce also the reduced SV partially. Therefore, the fact that MAP remained unchanged during HUT over a year after surgery, despite of the present medication status and the lower SV, have reminded us of improved baroreflex sensitivity over a year after CABG by elimination manner. The mechanisms of the present improvement over a year after surgery remains unclear, but an influence of blood volume did not relate the improvement at least.
SV was not recovered after 1.3–1.8 years after surgery in the patients. The reasons are not clear, but medications and low physical activity were possibly associated with the continued reduction [28, 29]. First, as mentioned above, b-blockers attenuate plasma renin activity, resulting in partially enhancing diuretic effect. The next, all patients completed whole rehabilitation program during the admission period, however, outpatient rehabilitation was not performed after discharge in our hospital. Even if exercise routine was provided after discharge according to the guidelines, exercise might not be performed as frequently under unsupervised situation [30]. The effects of home-based exercise on physical function could not be matched with that of the rehabilitation exercises under the supervision of therapists [31, 32]. Therefore, physical activity of the present patients might not be so large amount after discharge, resulting in prolonging hypovolemia ~ 1.5 years after the surgery, although again physical activity was not assessed in the present study.
In patients with cardiovascular disease, lower cardiorespiratory fitness, i.e. peak oxygen consumption rate (VO2peak), is related with greater risk for early mortality, future cardiovascular events, and higher healthcare costs [33]. Blood volume is one of the factors to determine VO2peak from the standpoint of exercise physiology [34]. In the present study, blood pressure response was recovered ~ 1.5 years after surgery, even lower blood volume compared with before surgery was suggested, contrary to our expectations. The prolonged hypovolemia, which is suggested by the present results, is still problem because it possibly disturbs an improvement of VO2peak.
Limitations
There were several limitations in the present study. The sample size was very small. Because this is a single-center study, the present results could highly depend on the operators. However, the fact that SV was lower even ~ 1.5 years after surgery is valuable. The physiological mechanism of the reduction and recovery of the MAP response after surgery is not completely clear, as baroreflex sensitivity was not assessed. Having said that, the present findings could be beneficial preliminary data for future prospective studies.
Perspectives
As suggested in studies of exercise intervention for patients 2 or 3 months after CABG, resting blood pressure did not alter significantly in the control group without exercise after the interventions [6, 7]. Other study also reported in CABG patients that 6-minute walking distance significantly increased 2 years after surgery in both sedentary and recreationally active (over 30 min activity three or more times per week) [8]. As described above, a strategy for improving SV, which might mean increasing blood volume, would achieve healthy life expectancy in these patients more than before.