© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Nitric oxide and efficiency of the right heart
Laboratory for Physiology, Institute for Cardiovascular Research, VU University medical center, Amsterdam, The Netherlands
* Tel.: +31 20 4448111; fax: +31 20 4448255. Email address: n.westerhof{at}vumc.nl
Received 30 August 2004; accepted 20 September 2004
See article by Setty et al. (pages 431–436) in this issue.
Several differences between right and left heart are known: the effect of cardiac contraction on coronary arterial inflow, autoregulation, and oxygen extraction. Setty et al. [1] show in their study the relationships between function and oxygen consumption of the right heart under control and ischemic conditions and the role of nitric oxide (NO). It turns out that these relationships also differ between left and right heart.
Coronary flow depends on perfusion pressure and cardiac oxygen consumption [2]. NO decreases vascular smooth muscle tone and thus modulates flow. NO also promotes vascular growth and affects cardiac function in terms of metabolism, contractility, rhythmicity, and growth [3]. Early studies on ischemia and the role of NO mainly emphasized the vasodilatory effect on the coronary vasculature and thus a protective role of NO. At higher concentrations, NO has a cGMP-independent negative inotropic effect [4]. NO synthase inhibition impairs the efficiency of oxidative metabolism and cardiac function, while during moderate ischemia, NO synthase appears not to be involved in cardiac metabolism [5]. It was also reported that NO does not modulate oxygen consumption and segment shortening during administration of calcium [6]. NO does not modify VO2 in exercise [7].
Presently, the accepted view is that NO increases left ventricular (LV) efficiency, i.e., allows greater external work for lower oxygen consumption, both acutely [8] and in the long term [9]. In moderate ischemia (perfusion pressure reduced to about 50%) with NO present, efficiency is almost 100% higher than after NO inhibition [8]. However, up until now almost all work reported pertains to the LV, and information on the right heart (right ventricle, RV) was missing. Setty et al. [1] now provide this information.
Cardiac efficiency is defined as the ratio of external work, equal to pressure times stroke volume (SV), to oxygen consumption (VO2) and can be based on direct measurements [10]. This global work has often been translated, for practical purposes, to local shortening times local, calculated stress or local shortening times ventricular pressure and is called the external work index [5,8]. The ratio of the external work index to local VO2 is called (local) efficiency. The demand–supply ratio is supposed to predict possible subendocardial ischemia in the left ventricle [11] and is rather generally used [12]. It is the ratio of mean systolic pressure (oxygen demand) to mean diastolic aortic pressure (oxygen supply). One implicit assumption is that coronary perfusion takes place in diastole only. This may be true for subendocardial layers of the LV but is not correct for the RV.
Setty et al. [1] use the so-called triple product, TP=HRdP/dtPs, with HR heart rate, dP/dt maximum rate of rise of ventricular pressure, and Ps systolic pressure, as a measure of oxygen demand, and they measure oxygen consumption, VO2. They define a demand–supply ratio as TP/VO2. Many hemodynamic parameters to estimate oxygen demand exist but all are to be considered with care [13].
The authors also use the term oxygen utilization efficiency for TP/VO2. If mean pulmonary artery pressure and SV or cardiac output had been measured, efficiency could have been derived directly. However, in their study the conditions are such that the TP and external work parallel each other. From their data we see that systolic RV pressure and heart rate are not affected by the interventions, implying that the pulmonary arterial vascular resistance did not change. This, in turn, means that external work is not changed. In other words, the oxygen utilization efficiency, TP/VO2, parallels efficiency.
When we compare the results of Setty et al. [1] to what is known about the left ventricle, we note the following:
- In the right heart, oxygen consumption is a little smaller when NO is present, but mechanical work is similar, and the efficiency is not changed by NO inhibition. In the left heart, the presence of NO does not affect VO2, but mechanical work is higher and thus efficiency is higher as well.
- In the right heart, mechanical parameters such as pressure and triple product are not affected by moderate ischemia, while VO2 is decreased, leading to increased efficiency. In the left heart, both external work and VO2 decrease in moderate ischemia, leaving efficiency virtually unaltered [8].
- In the right heart, oxygen consumption in the presence of NO is considerably lower than with NO inhibition, while mechanical parameters, including the TP, are not different. Therefore, NO makes the right heart in ischemia more efficient. In the ischemic left heart, with NO present, oxygen consumption is lower and mechanics, including external work, are higher, leading to a higher efficiency.
Thus, the results of Setty et al. [1] show that NO contributes to higher efficiency also in the right ventricle, especially during hypoperfusion. Why the muscle becomes more efficient awaits an explanation. The differences between right and left ventricle probably lie in the lower oxygen extraction and higher venous, and thus tissue PO2, in the right heart, especially with NO present (Fig. 1 of Ref. [1]). It should be worked out if this can quantitatively explain the differences, assuming that the cardiac muscle does not differ between right and left ventricle. NO donors may, in principle, be advantageous in moderate ischemia of the right heart.
 |
References |
|---|
 Top References |
|---|
- Setty S., Tune J.D., Downey H.F. Nitric oxide contributes to oxygen demand–supply balance in hypoperfused right ventricle. Cardiovasc. Res. (2004) 64:431–436.
[Abstract/Free Full Text] - Vergroesen I., Noble M.I.M., Wieringa P.A., Spaan J.A.E. Quantification of O2 consumption and arterial pressure as independent determinants of coronary flow. Am. J. Physiol. (1987) 252:H545–H553.[Web of Science][Medline]
- Brutsaert D.L. Cardiac endothelial–myocardial signaling: its role in cardiac growth, contractile performance and rhythmicity. Physiol. Rev. (2003) 83:59–115.
[Abstract/Free Full Text] - Decking U.K., Williams J.P., Dahmann R., Stumpe T., Kelm M., Schrader J. The nitric oxide-induced reduction in cardiac energy supply is not due to inhibition of creatine kinase. Cardiovasc. Res. (2001) 51:313–321.
[Abstract/Free Full Text] - Martin C., Schulz R., Post H., Gres P., Heusch G. Effect of NO synthase inhibition on myocardial metabolism during moderate ischemia. Am. J. Physiol. (2003) 284:H2320–H2324.[Web of Science]
- Crystal G.J., Zhou X., Gurevicius J., Czinn E.A., Salem M.R., Alam S., et al. Direct coronary vasomotor effects of sevoflurane and desflurane in in situ canine hearts. Anesthesiology (2000) 92:1103–1113.[CrossRef][Web of Science][Medline]
- Duncker D.J., Stubenitsky R., Tonino P.A.L., Verdouw P.D. Nitric oxide contributes to the regulation of vasomotor tone but does not modulate O(2)-consumption in exercising swine. Cardiovasc. Res. (2000) 47:738–748.
[Abstract/Free Full Text] - Heusch G., Post H., Michel M.C., Kelm M., Schulz R. Endogenous nitric oxide and myocardial adaptation to ischemia. Circ. Res. (2000) 87:146–152.
[Abstract/Free Full Text] - Post H., d'Agostino C., Lionetti V., Castellari M., Kang E.Y., Altarejos M., et al. Reduced left ventricular compliance and mechanical efficiency after prolonged inhibition of NO synthesis in conscious dogs. J. Physiol. (2003) 552:233–239.
[Abstract/Free Full Text] - Elzinga G., Westerhof N. Pump function of the feline left heart: changes with heart rate and its bearing on the energy balance. Cardiovasc. Res. (1980) 14:81–92.
[Abstract/Free Full Text] - Hoffman J.I.E., Buckberg G.D. The myocardial supply–demand ratio—a critical review. Am. J. Cardiol. (1978) 41:327–332.[CrossRef][Web of Science][Medline]
- Russell D.C., Balcon R. Haemodynamic effects on the myocardial blood flow supply/oxygen demand ratio in pacing induced angina pectoris. Cardiovasc. Res. (1978) 12:358–363.
[Abstract/Free Full Text] - Rooke G.A., Feigl E.O. Work as a correlate of canine left ventricular oxygen consumption, and the problem of catecholamine oxygen wasting. Circ. Res. (1982) 50:273–286.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||